首页 > 最新文献

EMBO Reports最新文献

英文 中文
Novel mechanisms of MITF regulation identified in a mouse suppressor screen. 在小鼠抑制因子筛选中发现新的 MITF 调节机制。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-21 DOI: 10.1038/s44319-024-00225-3
Hong Nhung Vu, Matti Már Valdimarsson, Sara Sigurbjörnsdóttir, Kristín Bergsteinsdóttir, Julien Debbache, Keren Bismuth, Deborah A Swing, Jón H Hallsson, Lionel Larue, Heinz Arnheiter, Neal G Copeland, Nancy A Jenkins, Petur O Heidarsson, Eiríkur Steingrímsson

MITF, a basic Helix-Loop-Helix Zipper (bHLHZip) transcription factor, plays vital roles in melanocyte development and functions as an oncogene. We perform a genetic screen for suppressors of the Mitf-associated pigmentation phenotype in mice and identify an intragenic Mitf mutation that terminates MITF at the K316 SUMOylation site, leading to loss of the C-end intrinsically disordered region (IDR). The resulting protein is more nuclear but less stable than wild-type MITF and retains DNA-binding ability. As a dimer, it can translocate wild-type and mutant MITF partners into the nucleus, improving its own stability thus ensuring nuclear MITF supply. smFRET analysis shows interactions between K316 SUMOylation and S409 phosphorylation sites across monomers; these interactions largely explain the observed effects. The recurrent melanoma-associated E318K mutation in MITF, which affects K316 SUMOylation, also alters protein regulation in concert with S409. This suggests that residues K316 and S409 of MITF are impacted by SUMOylation and phosphorylation, respectively, mediating effects on nuclear localization and stability through conformational changes. Our work provides a novel mechanism of genetic suppression, and an example of how apparently deleterious mutations lead to normal phenotypes.

MITF是一种基本螺旋-环-螺旋拉链(bHLHZip)转录因子,在黑色素细胞发育过程中发挥着重要作用,同时也是一种致癌基因。我们对小鼠Mitf相关色素沉着表型的抑制因子进行了基因筛选,发现了一种基因内Mitf突变,该突变在K316 SUMOylation位点终止了MITF,导致C端内紊乱区(IDR)缺失。由此产生的蛋白质比野生型 MITF 更具有核功能,但稳定性较差,并保留了 DNA 结合能力。smFRET 分析表明,K316 SUMOylation 和 S409 磷酸化位点之间存在跨单体的相互作用;这些相互作用在很大程度上解释了所观察到的效应。MITF 中反复出现的黑色素瘤相关 E318K 突变会影响 K316 SUMOylation,也会与 S409 一起改变蛋白质的调节。这表明,MITF的K316和S409残基分别受到SUMO化和磷酸化的影响,通过构象变化介导对核定位和稳定性的影响。我们的工作提供了一种新的遗传抑制机制,也提供了一个例子,说明表面上看似有害的突变是如何导致正常表型的。
{"title":"Novel mechanisms of MITF regulation identified in a mouse suppressor screen.","authors":"Hong Nhung Vu, Matti Már Valdimarsson, Sara Sigurbjörnsdóttir, Kristín Bergsteinsdóttir, Julien Debbache, Keren Bismuth, Deborah A Swing, Jón H Hallsson, Lionel Larue, Heinz Arnheiter, Neal G Copeland, Nancy A Jenkins, Petur O Heidarsson, Eiríkur Steingrímsson","doi":"10.1038/s44319-024-00225-3","DOIUrl":"10.1038/s44319-024-00225-3","url":null,"abstract":"<p><p>MITF, a basic Helix-Loop-Helix Zipper (bHLHZip) transcription factor, plays vital roles in melanocyte development and functions as an oncogene. We perform a genetic screen for suppressors of the Mitf-associated pigmentation phenotype in mice and identify an intragenic Mitf mutation that terminates MITF at the K316 SUMOylation site, leading to loss of the C-end intrinsically disordered region (IDR). The resulting protein is more nuclear but less stable than wild-type MITF and retains DNA-binding ability. As a dimer, it can translocate wild-type and mutant MITF partners into the nucleus, improving its own stability thus ensuring nuclear MITF supply. smFRET analysis shows interactions between K316 SUMOylation and S409 phosphorylation sites across monomers; these interactions largely explain the observed effects. The recurrent melanoma-associated E318K mutation in MITF, which affects K316 SUMOylation, also alters protein regulation in concert with S409. This suggests that residues K316 and S409 of MITF are impacted by SUMOylation and phosphorylation, respectively, mediating effects on nuclear localization and stability through conformational changes. Our work provides a novel mechanism of genetic suppression, and an example of how apparently deleterious mutations lead to normal phenotypes.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activation of an atypical plant NLR with an N-terminal deletion initiates cell death at the vacuole. 激活一种 N 端缺失的非典型植物 NLR 会导致细胞在液泡中死亡。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1038/s44319-024-00240-4
Sruthi Sunil, Simon Beeh, Eva Stöbbe, Kathrin Fischer, Franziska Wilhelm, Aron Meral, Celia Paris, Luisa Teasdale, Zhihao Jiang, Lisha Zhang, Moritz Urban, Emmanuel Aguilar Parras, Thorsten Nürnberger, Detlef Weigel, Rosa Lozano-Duran, Farid El Kasmi

Plants evolve nucleotide-binding leucine-rich repeat receptors (NLRs) to induce immunity. Activated coiled-coil (CC) domain containing NLRs (CNLs) oligomerize and form apparent cation channels promoting calcium influx and cell death, with the alpha-1 helix of the individual CC domains penetrating the plasma membranes. Some CNLs are characterized by putative N-myristoylation and S-acylation sites in their CC domain, potentially mediating permanent membrane association. Whether activated Potentially Membrane Localized NLRs (PMLs) mediate cell death and calcium influx in a similar way is unknown. We uncovered the cell-death function at the vacuole of an atypical but conserved Arabidopsis PML, PML5, which has a significant deletion in its CCG10/GA domain. Active PML5 oligomers localize in Golgi membranes and the tonoplast, alter vacuolar morphology, and induce cell death, with the short N-terminus being sufficient. Mutant analysis supports a potential role of PMLs in plant immunity. PML5-like deletions are found in several Brassicales paralogs, pointing to the evolutionary importance of this innovation. PML5, with its minimal CC domain, represents the first identified CNL utilizing vacuolar-stored calcium for cell death induction.

植物进化出核苷酸结合富亮氨酸重复受体(NLRs)来诱导免疫。活化的含盘绕线圈(CC)结构域的 NLRs(CNLs)会寡聚并形成明显的阳离子通道,促进钙离子流入和细胞死亡,单个 CC 结构域的 alpha-1 螺旋可穿透质膜。一些 CNL 的特征是其 CC 结构域中存在假定的 N-肉豆蔻酰化和 S-酰化位点,从而有可能介导永久性膜关联。活化的潜在膜定位 NLRs(PMLs)是否以类似方式介导细胞死亡和钙离子流入尚不清楚。我们发现了拟南芥一种非典型但保守的 PML(PML5)在液泡中的细胞死亡功能,该 PML5 的 CCG10/GA 结构域有显著缺失。活性 PML5 寡聚体定位在高尔基体膜和调质体中,改变液泡形态并诱导细胞死亡,短 N 端足以诱导细胞死亡。突变体分析支持 PML 在植物免疫中的潜在作用。在几种十字花科植物的旁系亲缘植物中发现了类似于 PML5 的缺失,这表明了这一创新在进化过程中的重要性。PML5 具有最小的 CC 结构域,是第一个利用液泡储存的钙诱导细胞死亡的 CNL。
{"title":"Activation of an atypical plant NLR with an N-terminal deletion initiates cell death at the vacuole.","authors":"Sruthi Sunil, Simon Beeh, Eva Stöbbe, Kathrin Fischer, Franziska Wilhelm, Aron Meral, Celia Paris, Luisa Teasdale, Zhihao Jiang, Lisha Zhang, Moritz Urban, Emmanuel Aguilar Parras, Thorsten Nürnberger, Detlef Weigel, Rosa Lozano-Duran, Farid El Kasmi","doi":"10.1038/s44319-024-00240-4","DOIUrl":"10.1038/s44319-024-00240-4","url":null,"abstract":"<p><p>Plants evolve nucleotide-binding leucine-rich repeat receptors (NLRs) to induce immunity. Activated coiled-coil (CC) domain containing NLRs (CNLs) oligomerize and form apparent cation channels promoting calcium influx and cell death, with the alpha-1 helix of the individual CC domains penetrating the plasma membranes. Some CNLs are characterized by putative N-myristoylation and S-acylation sites in their CC domain, potentially mediating permanent membrane association. Whether activated Potentially Membrane Localized NLRs (PMLs) mediate cell death and calcium influx in a similar way is unknown. We uncovered the cell-death function at the vacuole of an atypical but conserved Arabidopsis PML, PML5, which has a significant deletion in its CC<sub>G10/GA</sub> domain. Active PML5 oligomers localize in Golgi membranes and the tonoplast, alter vacuolar morphology, and induce cell death, with the short N-terminus being sufficient. Mutant analysis supports a potential role of PMLs in plant immunity. PML5-like deletions are found in several Brassicales paralogs, pointing to the evolutionary importance of this innovation. PML5, with its minimal CC domain, represents the first identified CNL utilizing vacuolar-stored calcium for cell death induction.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate. 4,5-二磷酸磷脂酰肌醇预激活 β-阿瑞斯汀-2的分子机制
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1038/s44319-024-00239-x
Kiae Kim, Ka Young Chung

Phosphorylated residues of G protein-coupled receptors bind to the N-domain of arrestin, resulting in the release of its C-terminus. This induces further allosteric conformational changes, such as polar core disruption, alteration of interdomain loops, and domain rotation, which transform arrestins into the receptor-activated state. It is widely accepted that arrestin activation occurs by conformational changes propagated from the N- to the C-domain. However, recent studies have revealed that binding of phosphatidylinositol 4,5-bisphosphate (PIP2) to the C-domain transforms arrestins into a pre-active state. Here, we aimed to elucidate the mechanisms underlying PIP2-induced arrestin pre-activation. We compare the conformational changes of β-arrestin-2 upon binding of PIP2 or phosphorylated C-tail peptide of vasopressin receptor type 2 using hydrogen/deuterium exchange mass spectrometry (HDX-MS). Introducing point mutations on the potential routes of the allosteric conformational changes and analyzing these mutant constructs with HDX-MS reveals that PIP2-binding at the C-domain affects the back loop, which destabilizes the gate loop and βXX to transform β-arrestin-2 into the pre-active state.

G 蛋白偶联受体的磷酸化残基与 arrestin 的 N 域结合,导致其 C 端释放。这会诱发进一步的异构构象变化,如极性核破坏、域间环改变和域旋转,从而将捕捉素转变为受体激活状态。人们普遍认为,捕获素的激活是通过从 N 域到 C 域的构象变化实现的。然而,最近的研究发现,磷脂酰肌醇 4,5-二磷酸(PIP2)与 C-结构域的结合会使捕捉素转变为前激活状态。在这里,我们旨在阐明 PIP2 诱导的 arrestins 预激活的机制。我们利用氢/氘交换质谱法(HDX-MS)比较了β-arrestin-2与PIP2或加压素受体2型磷酸化C尾肽结合时的构象变化。在异构构象变化的潜在途径上引入点突变,并用 HDX-MS 分析这些突变体构建物,发现 PIP2 结合 C 域会影响后环,从而破坏门环和 βXX 的稳定性,使 β-arrestin-2 转变为前活性状态。
{"title":"Molecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate.","authors":"Kiae Kim, Ka Young Chung","doi":"10.1038/s44319-024-00239-x","DOIUrl":"10.1038/s44319-024-00239-x","url":null,"abstract":"<p><p>Phosphorylated residues of G protein-coupled receptors bind to the N-domain of arrestin, resulting in the release of its C-terminus. This induces further allosteric conformational changes, such as polar core disruption, alteration of interdomain loops, and domain rotation, which transform arrestins into the receptor-activated state. It is widely accepted that arrestin activation occurs by conformational changes propagated from the N- to the C-domain. However, recent studies have revealed that binding of phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) to the C-domain transforms arrestins into a pre-active state. Here, we aimed to elucidate the mechanisms underlying PIP<sub>2</sub>-induced arrestin pre-activation. We compare the conformational changes of β-arrestin-2 upon binding of PIP<sub>2</sub> or phosphorylated C-tail peptide of vasopressin receptor type 2 using hydrogen/deuterium exchange mass spectrometry (HDX-MS). Introducing point mutations on the potential routes of the allosteric conformational changes and analyzing these mutant constructs with HDX-MS reveals that PIP<sub>2</sub>-binding at the C-domain affects the back loop, which destabilizes the gate loop and βXX to transform β-arrestin-2 into the pre-active state.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Goliath, meet David. 歌利亚,见大卫。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-16 DOI: 10.1038/s44319-024-00257-9
K Heran Darwin
{"title":"Goliath, meet David.","authors":"K Heran Darwin","doi":"10.1038/s44319-024-00257-9","DOIUrl":"10.1038/s44319-024-00257-9","url":null,"abstract":"","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis. mTOR 信号在脉管炎期间控制平滑肌细胞衍生的管腔肌成纤维细胞的形成。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-13 DOI: 10.1038/s44319-024-00251-1
Angus T Stock, Sarah Parsons, Jacinta A Hansen, Damian B D'Silva, Graham Starkey, Aly Fayed, Xin Yi Lim, Rohit D'Costa, Claire L Gordon, Ian P Wicks

The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived luminal myofibroblasts-in both mice and patients with KD, Takayasu's arteritis and Giant Cell arteritis-coincided with activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, SMC-specific deletion of mTOR signalling, or pharmacological inhibition, abrogated the emergence of luminal myofibroblasts. Thus, mTOR is an intrinsic and essential regulator of luminal myofibroblast formation that is activated in vasculitis patients and therapeutically tractable. These findings provide molecular insight into the pathogenesis of coronary artery stenosis and identify mTOR as a therapeutic target in vasculitis.

肌成纤维细胞在发炎血管内膜层的聚集是脉管炎的一种潜在灾难性并发症,可导致动脉狭窄和缺血。在这项研究中,我们调查了川崎病(KD)期间这些管腔肌成纤维细胞是如何发育的,川崎病是一种典型的涉及冠状动脉的儿科血管炎。通过在 KD 小鼠模型中进行系谱追踪研究,我们发现管腔肌成纤维细胞的发育独立于临近壁成纤维细胞和内皮细胞,而是来源于平滑肌细胞(SMC)。值得注意的是,在小鼠和 KD、高安氏动脉炎和巨细胞动脉炎患者中,SMC 衍生的管腔肌成纤维细胞的出现与雷帕霉素机制靶标(mTOR)信号通路的激活相一致。此外,SMC特异性缺失 mTOR 信号或药物抑制可抑制管腔肌成纤维细胞的出现。因此,mTOR 是管腔肌成纤维细胞形成的内在重要调节因子,它在脉管炎患者中被激活,并且具有治疗作用。这些发现从分子角度揭示了冠状动脉狭窄的发病机制,并确定了 mTOR 是脉管炎的治疗靶点。
{"title":"mTOR signalling controls the formation of smooth muscle cell-derived luminal myofibroblasts during vasculitis.","authors":"Angus T Stock, Sarah Parsons, Jacinta A Hansen, Damian B D'Silva, Graham Starkey, Aly Fayed, Xin Yi Lim, Rohit D'Costa, Claire L Gordon, Ian P Wicks","doi":"10.1038/s44319-024-00251-1","DOIUrl":"10.1038/s44319-024-00251-1","url":null,"abstract":"<p><p>The accumulation of myofibroblasts within the intimal layer of inflamed blood vessels is a potentially catastrophic complication of vasculitis, which can lead to arterial stenosis and ischaemia. In this study, we have investigated how these luminal myofibroblasts develop during Kawasaki disease (KD), a paediatric vasculitis typically involving the coronary arteries. By performing lineage tracing studies in a murine model of KD, we reveal that luminal myofibroblasts develop independently of adventitial fibroblasts and endothelial cells, and instead derive from smooth muscle cells (SMCs). Notably, the emergence of SMC-derived luminal myofibroblasts-in both mice and patients with KD, Takayasu's arteritis and Giant Cell arteritis-coincided with activation of the mechanistic target of rapamycin (mTOR) signalling pathway. Moreover, SMC-specific deletion of mTOR signalling, or pharmacological inhibition, abrogated the emergence of luminal myofibroblasts. Thus, mTOR is an intrinsic and essential regulator of luminal myofibroblast formation that is activated in vasculitis patients and therapeutically tractable. These findings provide molecular insight into the pathogenesis of coronary artery stenosis and identify mTOR as a therapeutic target in vasculitis.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression. Drp1 剪接变体调控卵巢癌线粒体动力学和肿瘤进展。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-27 DOI: 10.1038/s44319-024-00232-4
Zaineb Javed, Dong Hui Shin, Weihua Pan, Sierra R White, Amal Taher Elhaw, Yeon Soo Kim, Shriya Kamlapurkar, Ya-Yun Cheng, J Cory Benson, Ahmed Emam Abdelnaby, Rébécca Phaëton, Hong-Gang Wang, Shengyu Yang, Mara L G Sullivan, Claudette M St Croix, Simon C Watkins, Steven J Mullett, Stacy L Gelhaus, Nam Lee, Lan G Coffman, Katherine M Aird, Mohamed Trebak, Karthikeyan Mythreye, Vonn Walter, Nadine Hempel

Aberrant mitochondrial fission/fusion dynamics are frequently associated with pathologies, including cancer. We show that alternative splice variants of the fission protein Drp1 (DNM1L) contribute to the complexity of mitochondrial fission/fusion regulation in tumor cells. High tumor expression of the Drp1 alternative splice variant lacking exon 16 relative to other transcripts is associated with poor outcome in ovarian cancer patients. Lack of exon 16 results in Drp1 localization to microtubules and decreased association with mitochondrial fission sites, culminating in fused mitochondrial networks, enhanced respiration, changes in metabolism, and enhanced pro-tumorigenic phenotypes in vitro and in vivo. These effects are inhibited by siRNAs designed to specifically target the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the pathophysiological importance of Drp1 alternative splicing, highlight the divergent functions and consequences of changing the relative expression of Drp1 splice variants in tumor cells, and strongly warrant consideration of alternative splicing in future studies focused on Drp1.

线粒体裂变/融合动力学异常经常与包括癌症在内的各种病症有关。我们的研究表明,裂变蛋白 Drp1(DNM1L)的替代剪接变体增加了肿瘤细胞线粒体裂变/融合调控的复杂性。与其他转录本相比,缺乏第 16 号外显子的 Drp1 替代剪接变体的肿瘤高表达与卵巢癌患者的不良预后有关。缺乏第 16 号外显子会导致 Drp1 定位于微管,减少与线粒体裂变位点的结合,最终导致线粒体网络融合、呼吸增强、新陈代谢改变以及体外和体内促肿瘤表型增强。这些效应会被设计为特异性靶向缺乏第 16 号外显子的内源性表达转录本的 siRNA 所抑制。此外,缺乏第 16 号外显子会抑制线粒体在促凋亡刺激下的分裂,并导致对化疗药物的敏感性降低。这些数据强调了 Drp1 替代剪接在病理生理学上的重要性,突出了改变肿瘤细胞中 Drp1 剪接变体的相对表达所产生的不同功能和后果,并强烈建议在今后以 Drp1 为重点的研究中考虑替代剪接。
{"title":"Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression.","authors":"Zaineb Javed, Dong Hui Shin, Weihua Pan, Sierra R White, Amal Taher Elhaw, Yeon Soo Kim, Shriya Kamlapurkar, Ya-Yun Cheng, J Cory Benson, Ahmed Emam Abdelnaby, Rébécca Phaëton, Hong-Gang Wang, Shengyu Yang, Mara L G Sullivan, Claudette M St Croix, Simon C Watkins, Steven J Mullett, Stacy L Gelhaus, Nam Lee, Lan G Coffman, Katherine M Aird, Mohamed Trebak, Karthikeyan Mythreye, Vonn Walter, Nadine Hempel","doi":"10.1038/s44319-024-00232-4","DOIUrl":"10.1038/s44319-024-00232-4","url":null,"abstract":"<p><p>Aberrant mitochondrial fission/fusion dynamics are frequently associated with pathologies, including cancer. We show that alternative splice variants of the fission protein Drp1 (DNM1L) contribute to the complexity of mitochondrial fission/fusion regulation in tumor cells. High tumor expression of the Drp1 alternative splice variant lacking exon 16 relative to other transcripts is associated with poor outcome in ovarian cancer patients. Lack of exon 16 results in Drp1 localization to microtubules and decreased association with mitochondrial fission sites, culminating in fused mitochondrial networks, enhanced respiration, changes in metabolism, and enhanced pro-tumorigenic phenotypes in vitro and in vivo. These effects are inhibited by siRNAs designed to specifically target the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the pathophysiological importance of Drp1 alternative splicing, highlight the divergent functions and consequences of changing the relative expression of Drp1 splice variants in tumor cells, and strongly warrant consideration of alternative splicing in future studies focused on Drp1.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HIV-1 Vpu induces neurotoxicity by promoting Caspase 3-dependent cleavage of TDP-43. HIV-1 Vpu 通过促进 Caspase 3 依赖性裂解 TDP-43 来诱导神经毒性。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1038/s44319-024-00238-y
Jiaxin Yang, Yan Li, Huili Li, Haichen Zhang, Haoran Guo, Xiangyu Zheng, Xiao-Fang Yu, Wei Wei

Despite the efficacy of highly active antiretroviral therapy in controlling the incidence and mortality of AIDS, effective interventions for HIV-1-induced neurological damage and cognitive impairment remain elusive. In this study, we found that HIV-1 infection can induce proteolytic cleavage and aberrant aggregation of TAR DNA-binding protein 43 (TDP-43), a pathological protein associated with various severe neurological disorders. The HIV-1 accessory protein Vpu was found to be responsible for the cleavage of TDP-43, as ectopic expression of Vpu alone was sufficient to induce TDP-43 cleavage, whereas HIV-1 lacking Vpu failed to cleave TDP-43. Mechanistically, the cleavage of TDP-43 at Asp89 by HIV-1 relies on Vpu-mediated activation of Caspase 3, and pharmacological inhibition of Caspase 3 activity effectively suppressed the HIV-1-induced aggregation and neurotoxicity of TDP-43. Overall, these results suggest that TDP-43 is a conserved host target of HIV-1 Vpu and provide evidence for the involvement of TDP-43 dysregulation in the neural pathogenesis of HIV-1.

尽管高效抗逆转录病毒疗法能有效控制艾滋病的发病率和死亡率,但针对 HIV-1 引起的神经系统损伤和认知障碍的有效干预措施却仍遥遥无期。在这项研究中,我们发现 HIV-1 感染可诱导 TAR DNA 结合蛋白 43(TDP-43)的蛋白水解和异常聚集,而 TAR DNA 结合蛋白 43 是一种与各种严重神经系统疾病相关的病理蛋白。研究发现,HIV-1辅助蛋白Vpu是TDP-43裂解的元凶,因为仅异位表达Vpu就足以诱导TDP-43裂解,而缺乏Vpu的HIV-1则无法裂解TDP-43。从机理上讲,HIV-1 在 Asp89 处裂解 TDP-43 依赖于 Vpu 介导的 Caspase 3 激活,而药物抑制 Caspase 3 的活性可有效抑制 HIV-1 诱导的 TDP-43 聚集和神经毒性。总之,这些结果表明,TDP-43是HIV-1 Vpu的一个保守宿主靶标,并为TDP-43失调参与HIV-1的神经发病机制提供了证据。
{"title":"HIV-1 Vpu induces neurotoxicity by promoting Caspase 3-dependent cleavage of TDP-43.","authors":"Jiaxin Yang, Yan Li, Huili Li, Haichen Zhang, Haoran Guo, Xiangyu Zheng, Xiao-Fang Yu, Wei Wei","doi":"10.1038/s44319-024-00238-y","DOIUrl":"10.1038/s44319-024-00238-y","url":null,"abstract":"<p><p>Despite the efficacy of highly active antiretroviral therapy in controlling the incidence and mortality of AIDS, effective interventions for HIV-1-induced neurological damage and cognitive impairment remain elusive. In this study, we found that HIV-1 infection can induce proteolytic cleavage and aberrant aggregation of TAR DNA-binding protein 43 (TDP-43), a pathological protein associated with various severe neurological disorders. The HIV-1 accessory protein Vpu was found to be responsible for the cleavage of TDP-43, as ectopic expression of Vpu alone was sufficient to induce TDP-43 cleavage, whereas HIV-1 lacking Vpu failed to cleave TDP-43. Mechanistically, the cleavage of TDP-43 at Asp89 by HIV-1 relies on Vpu-mediated activation of Caspase 3, and pharmacological inhibition of Caspase 3 activity effectively suppressed the HIV-1-induced aggregation and neurotoxicity of TDP-43. Overall, these results suggest that TDP-43 is a conserved host target of HIV-1 Vpu and provide evidence for the involvement of TDP-43 dysregulation in the neural pathogenesis of HIV-1.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L. DELTEX 泛素 E3 连接酶 DTX3L 对核酸的泛素化。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1038/s44319-024-00235-1
Kang Zhu, Chatrin Chatrin, Marcin J Suskiewicz, Vincent Aucagne, Benjamin Foster, Benedikt M Kessler, Ian Gibbs-Seymour, Dragana Ahel, Ivan Ahel

The recent discovery of non-proteinaceous ubiquitylation substrates broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated via ester bond formation. DTX3L, a member of the DELTEX family E3 ubiquitin ligases, ubiquitylates DNA and RNA in vitro and that this activity is shared with DTX3, but not with the other DELTEX family members DTX1, DTX2 and DTX4. DTX3L shows preference for the 3'-terminal adenosine over other nucleotides. In addition, we demonstrate that ubiquitylation of nucleic acids is reversible by DUBs such as USP2, JOSD1 and SARS-CoV-2 PLpro. Overall, our study proposes reversible ubiquitylation of nucleic acids in vitro and discusses its potential functional implications.

最近发现的非蛋白质泛素化底物拓宽了我们对这种修饰的认识,使其超越了传统的蛋白质靶标。然而,其他类型底物的存在仍然难以捉摸。在这里,我们提出了核酸也可以通过酯键形成直接泛素化的证据。DTX3L 是 DELTEX 家族 E3 泛素连接酶的成员,它能在体外泛素化 DNA 和 RNA,而且这种活性与 DTX3 共享,但与 DELTEX 家族的其他成员 DTX1、DTX2 和 DTX4 并不共享。与其他核苷酸相比,DTX3L 对 3'-terminal adenosine 更有偏好。此外,我们还证明了核酸的泛素化是可以被 USP2、JOSD1 和 SARS-CoV-2 PLpro 等 DUBs 逆转的。总之,我们的研究提出了核酸在体外的可逆泛素化,并讨论了其潜在的功能意义。
{"title":"Ubiquitylation of nucleic acids by DELTEX ubiquitin E3 ligase DTX3L.","authors":"Kang Zhu, Chatrin Chatrin, Marcin J Suskiewicz, Vincent Aucagne, Benjamin Foster, Benedikt M Kessler, Ian Gibbs-Seymour, Dragana Ahel, Ivan Ahel","doi":"10.1038/s44319-024-00235-1","DOIUrl":"10.1038/s44319-024-00235-1","url":null,"abstract":"<p><p>The recent discovery of non-proteinaceous ubiquitylation substrates broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated via ester bond formation. DTX3L, a member of the DELTEX family E3 ubiquitin ligases, ubiquitylates DNA and RNA in vitro and that this activity is shared with DTX3, but not with the other DELTEX family members DTX1, DTX2 and DTX4. DTX3L shows preference for the 3'-terminal adenosine over other nucleotides. In addition, we demonstrate that ubiquitylation of nucleic acids is reversible by DUBs such as USP2, JOSD1 and SARS-CoV-2 PLpro. Overall, our study proposes reversible ubiquitylation of nucleic acids in vitro and discusses its potential functional implications.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets. 一种新型细菌效应蛋白介导 ER-LD 膜接触以调节宿主脂滴。
IF 6.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-27 DOI: 10.1038/s44319-024-00266-8
Rajendra Kumar Angara, Arif Sadi, Stacey D Gilk

Effective intracellular communication between cellular organelles occurs at dedicated membrane contact sites (MCSs). Tether proteins are responsible for the establishment of MCSs, enabling direct communication between organelles to ensure organelle function and host cell homeostasis. While recent research has identified tether proteins in several bacterial pathogens, their functions have predominantly been associated with mediating inter-organelle communication between the bacteria containing vacuole (BCV) and the host endoplasmic reticulum (ER). Here, we identify a novel bacterial effector protein, CbEPF1, which acts as a molecular tether beyond the confines of the BCV and facilitates interactions between host cell organelles. Coxiella burnetii, an obligate intracellular bacterial pathogen, encodes the FFAT motif-containing protein CbEPF1 which localizes to host lipid droplets (LDs). CbEPF1 establishes inter-organelle contact sites between host LDs and the ER through its interactions with VAP family proteins. Intriguingly, CbEPF1 modulates growth of host LDs in a FFAT motif-dependent manner. These findings highlight the potential for bacterial effector proteins to impact host cellular homeostasis by manipulating inter-organelle communication beyond conventional BCVs.

细胞器之间的有效细胞内通讯发生在专用的膜接触点(MCS)上。系链蛋白负责建立 MCS,使细胞器之间能够直接交流,从而确保细胞器的功能和宿主细胞的稳态。虽然最近的研究在几种细菌病原体中发现了系链蛋白,但它们的功能主要与介导含菌泡 (BCV) 和宿主内质网 (ER) 之间的细胞器间通信有关。在这里,我们发现了一种新型细菌效应蛋白 CbEPF1,它在 BCV 的限制范围之外充当分子系链,促进宿主细胞器之间的相互作用。烧伤柯西氏菌是一种强制性细胞内细菌病原体,它编码的含FFAT基序的蛋白质CbEPF1可定位到宿主脂滴(LD)上。CbEPF1 通过与 VAP 家族蛋白相互作用,在宿主脂滴和 ER 之间建立细胞器间的接触点。耐人寻味的是,CbEPF1以一种依赖于FFAT图案的方式调节宿主LDs的生长。这些发现凸显了细菌效应蛋白通过操纵细胞器间通信影响宿主细胞稳态的潜力,而不是传统的 BCV。
{"title":"A novel bacterial effector protein mediates ER-LD membrane contacts to regulate host lipid droplets.","authors":"Rajendra Kumar Angara, Arif Sadi, Stacey D Gilk","doi":"10.1038/s44319-024-00266-8","DOIUrl":"10.1038/s44319-024-00266-8","url":null,"abstract":"<p><p>Effective intracellular communication between cellular organelles occurs at dedicated membrane contact sites (MCSs). Tether proteins are responsible for the establishment of MCSs, enabling direct communication between organelles to ensure organelle function and host cell homeostasis. While recent research has identified tether proteins in several bacterial pathogens, their functions have predominantly been associated with mediating inter-organelle communication between the bacteria containing vacuole (BCV) and the host endoplasmic reticulum (ER). Here, we identify a novel bacterial effector protein, CbEPF1, which acts as a molecular tether beyond the confines of the BCV and facilitates interactions between host cell organelles. Coxiella burnetii, an obligate intracellular bacterial pathogen, encodes the FFAT motif-containing protein CbEPF1 which localizes to host lipid droplets (LDs). CbEPF1 establishes inter-organelle contact sites between host LDs and the ER through its interactions with VAP family proteins. Intriguingly, CbEPF1 modulates growth of host LDs in a FFAT motif-dependent manner. These findings highlight the potential for bacterial effector proteins to impact host cellular homeostasis by manipulating inter-organelle communication beyond conventional BCVs.</p>","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity. miRNA 介导的 gephyrin 合成控制驱动持续的抑制性突触可塑性。
IF 7.7 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-18 DOI: 10.1038/s44319-024-00253-z
Theresa M Welle,Dipen Rajgor,Dean J Kareemo,Joshua D Garcia,Sarah M Zych,Sarah E Wolfe,Sara E Gookin,Tyler P Martinez,Mark L Dell'Acqua,Christopher P Ford,Matthew J Kennedy,Katharine R Smith
Activity-dependent protein synthesis is crucial for long-lasting forms of synaptic plasticity. However, our understanding of translational mechanisms controlling GABAergic synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the mechanisms controlling plasticity-induced gephyrin translation remain unknown. We identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting inhibitory synaptic structure and function. iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and promoting de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Together, we delineate a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.
依赖活动的蛋白质合成对于突触可塑性的持久形式至关重要。然而,我们对控制 GABA 能突触的翻译机制了解有限。一种独特形式的抑制性长期电位(iLTP)可增强突触后的 GABAARs 簇和主要抑制性支架 gephyrin,从而促进持续的突触强化。虽然我们以前发现持续的 iLTP 需要 mRNA 翻译,但控制可塑性诱导的 gephyrin 翻译的机制仍然未知。我们发现 miR153 是 Gphn mRNA 翻译的新型调控因子,它控制着 gephyrin 蛋白水平和突触集群,最终影响抑制性突触的结构和功能。iLTP 诱导下调 miR153,逆转其对 Gphn mRNA 翻译的抑制,促进 iLTP 期间 gephyrin 蛋白的新合成和突触集群。最后,我们发现 iLTP 期间 miR153 表达的减少是由涉及钙神经蛋白、NFAT 和 HDAC 的兴奋-转录耦合途径驱动的,该途径也控制着依赖 miRNA 的 GABAARs 上调。综上所述,我们勾勒出了一种依赖于 miRNA 的转录后机制,该机制控制着关键突触支架 gephyrin 的表达,并可能与平行的 miRNA 通路汇聚在一起,协调基因上调以维持抑制性突触可塑性。
{"title":"miRNA-mediated control of gephyrin synthesis drives sustained inhibitory synaptic plasticity.","authors":"Theresa M Welle,Dipen Rajgor,Dean J Kareemo,Joshua D Garcia,Sarah M Zych,Sarah E Wolfe,Sara E Gookin,Tyler P Martinez,Mark L Dell'Acqua,Christopher P Ford,Matthew J Kennedy,Katharine R Smith","doi":"10.1038/s44319-024-00253-z","DOIUrl":"https://doi.org/10.1038/s44319-024-00253-z","url":null,"abstract":"Activity-dependent protein synthesis is crucial for long-lasting forms of synaptic plasticity. However, our understanding of translational mechanisms controlling GABAergic synapses is limited. One distinct form of inhibitory long-term potentiation (iLTP) enhances postsynaptic clusters of GABAARs and the primary inhibitory scaffold, gephyrin, to promote sustained synaptic strengthening. While we previously found that persistent iLTP requires mRNA translation, the mechanisms controlling plasticity-induced gephyrin translation remain unknown. We identify miR153 as a novel regulator of Gphn mRNA translation which controls gephyrin protein levels and synaptic clustering, ultimately impacting inhibitory synaptic structure and function. iLTP induction downregulates miR153, reversing its translational suppression of Gphn mRNA and promoting de novo gephyrin protein synthesis and synaptic clustering during iLTP. Finally, we find that reduced miR153 expression during iLTP is driven by an excitation-transcription coupling pathway involving calcineurin, NFAT and HDACs, which also controls the miRNA-dependent upregulation of GABAARs. Together, we delineate a miRNA-dependent post-transcriptional mechanism that controls the expression of the key synaptic scaffold, gephyrin, and may converge with parallel miRNA pathways to coordinate gene upregulation to maintain inhibitory synaptic plasticity.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
EMBO Reports
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1