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Antiterminator LoaP loads onto RNA to chase a runaway RNA polymerase 反终结者 LoaP 加载到 RNA 上,追逐失控的 RNA 聚合酶
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1016/j.str.2024.07.024
Bing Wang, Irina Artsimovitch

In this issue of Structure, Elghondakly et al.1 present the crystal structure of Thermoanaerobacter pseudethanolicus antiterminator LoaP, a member of a ubiquitous family of NusG transcription factors, bound to its target, a dfn RNA hairpin. LoaP uses RNA as a recognition determinant, which is unique among NusG paralogs and makes unusual contacts in the major groove of the RNA.

在本期《结构》杂志上,Elghondakly 等人1 发现了假乙醇嗜热杆菌(Thermoanaerobacter pseudethanolicus)反终结因子 LoaP 与其目标(dfn RNA 发夹)结合的晶体结构,LoaP 是无处不在的 NusG 转录因子家族的一员。LoaP 使用 RNA 作为识别决定因子,这在 NusG 旁系亲属中是独一无二的,并且在 RNA 的主要沟槽中进行不寻常的接触。
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引用次数: 0
Crystal structure of lipase from Pseudomonas aeruginosa reveals an unusual catalytic triad conformation. 铜绿假单胞菌脂肪酶的晶体结构揭示了不寻常的催化三元构象。
IF 4.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 Epub Date: 2024-07-17 DOI: 10.1016/j.str.2024.06.014
Gang Xu, Hua Guo, Zhonglang Yu, Shulin Wang, Dandan Shen, Lirong Yang, Jianping Wu, Binbin Chen, Haoran Yu

The Pseudomonas aeruginosa lipase PaL catalyzes the stereoselective hydrolysis of menthyl propionate to produce L-menthol. The lack of a three-dimensional structure of PaL has so far prevented a detailed understanding of its stereoselective reaction mechanism. Here, the crystal structure of PaL was determined at a resolution of 1.80 Å by single-wavelength anomalous diffraction. In the apo-PaL structure, the catalytic His302 is located in a long loop on the surface that is solvent exposed. His302 is distant from the other two catalytic residues, Asp274 and Ser164. This configuration of catalytic residues is unusual for lipases. Using metadynamics simulations, we observed that the enzyme undergoes a significant conformational change upon ligand binding. We also explored the catalytic and stereoselectivity mechanisms of PaL by all-atom molecular dynamics simulations. These findings could guide the engineering of PaL with an improved diastereoselectivity for L-menthol production.

铜绿假单胞菌脂肪酶 PaL 可催化丙酸薄荷酯的立体选择性水解,生成 L-薄荷醇。迄今为止,由于缺乏 PaL 的三维结构,人们无法详细了解其立体选择性反应机制。在此,我们通过单波长反常衍射测定了 PaL 的晶体结构,其分辨率为 1.80 Å。在apo-PaL结构中,催化剂His302位于表面的一个长环上,该环暴露在溶剂中。His302 与另外两个催化残基 Asp274 和 Ser164 相距甚远。这种催化残基的构型在脂肪酶中并不多见。通过元动力学模拟,我们观察到该酶在与配体结合后发生了显著的构象变化。我们还通过全原子分子动力学模拟探索了 PaL 的催化和立体选择性机制。这些发现可以指导人们设计出具有更好非对映选择性的 PaL,用于生产 L-薄荷醇。
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引用次数: 0
Structural review of SARS-CoV-2 antiviral targets SARS-CoV-2 抗病毒靶标的结构回顾
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1016/j.str.2024.08.005
Wen Cui, Yinkai Duan, Yan Gao, Wei Wang, Haitao Yang

The coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents the most disastrous infectious disease pandemic of the past century. As a member of the Betacoronavirus genus, the SARS-CoV-2 genome encodes a total of 29 proteins. The spike protein, RNA-dependent RNA polymerase, and proteases play crucial roles in the virus replication process and are promising targets for drug development. In recent years, structural studies of these viral proteins and of their complexes with antibodies and inhibitors have provided valuable insights into their functions and laid a solid foundation for drug development. In this review, we summarize the structural features of these proteins and discuss recent progress in research regarding therapeutic development, highlighting mechanistically representative molecules and those that have already been approved or are under clinical investigation.

冠状病毒病 2019(COVID-19)是由严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)引起的疾病,是上个世纪最具灾难性的传染病大流行。作为 Betacoronavirus 属的一员,SARS-CoV-2 基因组共编码 29 种蛋白质。尖峰蛋白、RNA 依赖性 RNA 聚合酶和蛋白酶在病毒复制过程中起着至关重要的作用,是很有希望的药物开发目标。近年来,对这些病毒蛋白及其与抗体和抑制剂复合物的结构研究为了解其功能提供了宝贵的信息,为药物开发奠定了坚实的基础。在这篇综述中,我们总结了这些蛋白质的结构特征,并讨论了有关治疗开发的最新研究进展,重点介绍了在机理上具有代表性的分子以及那些已经获得批准或正在进行临床研究的分子。
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引用次数: 0
Binding of steroid substrates reveals the key to the productive transition of the cytochrome P450 OleP. 类固醇底物的结合揭示了细胞色素 P450 OleP 生产转换的关键。
IF 4.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 Epub Date: 2024-07-05 DOI: 10.1016/j.str.2024.06.005
Antonella Costanzo, Francesca Fata, Ida Freda, Maria Laura De Sciscio, Elena Gugole, Giovanni Bulfaro, Matteo Di Renzo, Luca Barbizzi, Cécile Exertier, Giacomo Parisi, Marco D'Abramo, Beatrice Vallone, Carmelinda Savino, Linda Celeste Montemiglio

OleP is a bacterial cytochrome P450 involved in oleandomycin biosynthesis as it catalyzes regioselective epoxidation on macrolide intermediates. OleP has recently been reported to convert lithocholic acid (LCA) into murideoxycholic acid through a highly regioselective reaction and to unspecifically hydroxylate testosterone (TES). Since LCA and TES mainly differ by the substituent group at the C17, here we used X-ray crystallography, equilibrium binding assays, and molecular dynamics simulations to investigate the molecular basis of the diverse reactivity observed with the two steroids. We found that the differences in the structure of TES and LCA affect the capability of these molecules to directly form hydrogen bonds with N-terminal residues of OleP internal helix I. The establishment of these contacts, by promoting the bending of helix I, fosters an efficient trigger of the open-to-closed structural transition that occurs upon substrate binding to OleP and contributes to the selectivity of the subsequent monooxygenation reaction.

OleP 是一种细菌细胞色素 P450,参与油霉素的生物合成,催化大环内酯中间体的区域选择性环氧化反应。最近有报道称,OleP 可通过高区域选择性反应将石胆酸(LCA)转化为鼠去氧胆酸,并对睾酮(TES)进行非特异性羟化。由于 LCA 和 TES 的主要区别在于 C17 上的取代基,因此我们在此使用 X 射线晶体学、平衡结合试验和分子动力学模拟来研究观察到的这两种类固醇的不同反应性的分子基础。我们发现,TES 和 LCA 结构的差异影响了这些分子与 OleP 内部螺旋 I 的 N 端残基直接形成氢键的能力。这些接触的建立促进了螺旋 I 的弯曲,从而有效地触发了底物与 OleP 结合后发生的从开放到封闭的结构转变,并提高了后续单氧反应的选择性。
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引用次数: 0
RNA dynamics from experimental and computational approaches 从实验和计算方法看 RNA 动力学
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1016/j.str.2024.07.019
Giovanni Bussi, Massimiliano Bonomi, Paraskevi Gkeka, Michael Sattler, Hashim M. Al-Hashimi, Pascal Auffinger, Maria Duca, Yann Foricher, Danny Incarnato, Alisha N. Jones, Serdal Kirmizialtin, Miroslav Krepl, Modesto Orozco, Giulia Palermo, Samuela Pasquali, Loïc Salmon, Harald Schwalbe, Eric Westhof, Martin Zacharias

Conformational dynamics is crucial for the biological function of RNA molecules and for their potential as therapeutic targets. This meeting report outlines key “take-home” messages that emerged from the presentations and discussions during the CECAM workshop “RNA dynamics from experimental and computational approaches” in Paris, June 26–28, 2023.

构象动力学对 RNA 分子的生物功能及其作为治疗靶点的潜力至关重要。本会议报告概述了 2023 年 6 月 26-28 日在巴黎举行的 CECAM "从实验和计算方法看 RNA 动态 "研讨会上的发言和讨论所产生的主要 "收获"。
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引用次数: 0
Structure of calcineurin bound to PI4KA reveals dual interface in both PI4KA and FAM126A 与 PI4KA 结合的钙神经蛋白的结构揭示了 PI4KA 和 FAM126A 的双重界面
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-30 DOI: 10.1016/j.str.2024.08.007
Alexandria L. Shaw, Sushant Suresh, Matthew A.H. Parson, Noah J. Harris, Meredith L. Jenkins, Calvin K. Yip, John E. Burke

Phosphatidylinositol 4-kinase alpha (PI4KA) maintains the phosphatidylinositol 4-phosphate (PI4P) and phosphatidylserine pools of the plasma membrane. A key regulator of PI4KA is its association into a complex with TTC7 and FAM126 proteins. This complex can be regulated by the CNAβ1 isoform of the phosphatase calcineurin. We previously identified that CNAβ1 directly binds to FAM126A. Here, we report a cryoelectron microscopic (cryo-EM) structure of a truncated PI4KA complex bound to calcineurin, revealing a unique direct interaction between PI4KA and calcineurin. Hydrogen deuterium exchange mass spectrometry (HDX-MS) and computational analysis show that calcineurin forms a complex with an evolutionarily conserved IKISVT sequence in PI4KA’s horn domain. We also characterized conserved LTLT and PSISIT calcineurin binding sequences in the C terminus of FAM126A. These dual sites in PI4KA and FAM126A are both in close proximity to phosphorylation sites in the PI4KA complex, suggesting key roles of calcineurin-regulated phosphosites in PI4KA regulation. This work reveals novel insight into how calcineurin can regulate PI4KA activity.

磷脂酰肌醇 4-激酶α(PI4KA)维持着质膜的磷脂酰肌醇 4-磷酸(PI4P)和磷脂酰丝氨酸池。PI4KA 的一个关键调节因子是它与 TTC7 和 FAM126 蛋白形成的复合物。该复合物可由磷酸酶钙调磷酸酶的 CNAβ1 异构体调节。我们之前发现 CNAβ1 可直接与 FAM126A 结合。在这里,我们报告了与钙调素结合的截短 PI4KA 复合物的冷冻电镜(cryo-EM)结构,揭示了 PI4KA 与钙调素之间独特的直接相互作用。氢氘交换质谱(HDX-MS)和计算分析表明,钙调素与 PI4KA 角域中进化保守的 IKISVT 序列形成复合物。我们还鉴定了 FAM126A C 末端保守的 LTLT 和 PSISIT 钙调素结合序列。PI4KA 和 FAM126A 中的这些双重位点都非常接近 PI4KA 复合物中的磷酸化位点,这表明钙神经蛋白调控的磷酸化位点在 PI4KA 的调控中起着关键作用。这项工作揭示了钙调素如何调控 PI4KA 活性的新见解。
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引用次数: 0
Cryo-EM structures of a bathy phytochrome histidine kinase reveal a unique light-dependent activation mechanism 一种水底植物色素组氨酸激酶的低温电子显微镜结构揭示了一种独特的光依赖性激活机制
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-30 DOI: 10.1016/j.str.2024.08.008
Szabolcs Bódizs, Petra Mészáros, Lukas Grunewald, Heikki Takala, Sebastian Westenhoff

Phytochromes are photoreceptor proteins in plants, fungi, and bacteria. They can adopt two photochromic states with differential biochemical responses. The structural changes transducing the signal from the chromophore to the biochemical output modules are poorly understood due to challenges in capturing structures of the dynamic, full-length protein. Here, we present cryoelectron microscopy (cryo-EM) structures of the phytochrome from Pseudomonas aeruginosa (PaBphP) in its resting (Pfr) and photoactivated (Pr) state. The kinase-active Pr state has an asymmetric, dimeric structure, whereas the kinase-inactive Pfr state opens up. This behavior is different from other known phytochromes and we explain it with the unusually short connection between the photosensory and output modules. Multiple sequence alignment of this region suggests evolutionary optimization for different modes of signal transduction in sensor proteins. The results establish a new mechanism for light-sensing by phytochrome histidine kinases and provide input for the design of optogenetic phytochrome variants.

植物色素是植物、真菌和细菌中的感光蛋白质。它们可以采用两种光致变色状态,并做出不同的生化反应。由于难以捕捉动态全长蛋白质的结构,人们对从发色团向生化输出模块传递信号的结构变化知之甚少。在这里,我们展示了铜绿假单胞菌的植物色素(PaBphP)在静止(Pfr)和光激活(Pr)状态下的冷冻电子显微镜(cryo-EM)结构。激酶激活状态的 Pr 具有不对称的二聚体结构,而激酶不激活状态的 Pfr 则是开放的。这种行为不同于其他已知的植物色素,我们用光敏模块和输出模块之间异常短的连接来解释这种行为。该区域的多重序列比对表明,传感器蛋白质中不同的信号转导模式在进化过程中得到了优化。这些结果为植物色素组氨酸激酶的光感应建立了一种新的机制,并为设计光遗传植物色素变体提供了参考。
{"title":"Cryo-EM structures of a bathy phytochrome histidine kinase reveal a unique light-dependent activation mechanism","authors":"Szabolcs Bódizs, Petra Mészáros, Lukas Grunewald, Heikki Takala, Sebastian Westenhoff","doi":"10.1016/j.str.2024.08.008","DOIUrl":"https://doi.org/10.1016/j.str.2024.08.008","url":null,"abstract":"<p>Phytochromes are photoreceptor proteins in plants, fungi, and bacteria. They can adopt two photochromic states with differential biochemical responses. The structural changes transducing the signal from the chromophore to the biochemical output modules are poorly understood due to challenges in capturing structures of the dynamic, full-length protein. Here, we present cryoelectron microscopy (cryo-EM) structures of the phytochrome from <em>Pseudomonas aeruginosa</em> (<em>Pa</em>BphP) in its resting (Pfr) and photoactivated (Pr) state. The kinase-active Pr state has an asymmetric, dimeric structure, whereas the kinase-inactive Pfr state opens up. This behavior is different from other known phytochromes and we explain it with the unusually short connection between the photosensory and output modules. Multiple sequence alignment of this region suggests evolutionary optimization for different modes of signal transduction in sensor proteins. The results establish a new mechanism for light-sensing by phytochrome histidine kinases and provide input for the design of optogenetic phytochrome variants.</p>","PeriodicalId":22168,"journal":{"name":"Structure","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Structural insights into the convergent evolution of sulfoxide synthase EgtB-IV, an ergothioneine-biosynthetic homolog of ovothiol synthase OvoA 亚砜合成酶EgtB-IV(麦角硫因生物合成同源物卵硫醇合成酶OvoA)趋同进化的结构见解
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-30 DOI: 10.1016/j.str.2024.08.006
Kendra A. Ireland, Chase M. Kayrouz, Marissa L. Abbott, Mohammad R. Seyedsayamdost, Katherine M. Davis

Non-heme iron-dependent sulfoxide/selenoxide synthases (NHISS) constitute a unique metalloenzyme class capable of installing a C–S/Se bond onto histidine to generate thio/selenoimidazole antioxidants, such as ergothioneine and ovothiol. These natural products are increasingly recognized for their health benefits. Among associated ergothioneine-biosynthetic enzymes, type IV EgtBs stand out, as they exhibit low sequence similarity with other EgtB subfamilies due to their recent divergence from the ovothiol-biosynthetic enzyme OvoA. Herein, we present crystal structures of two representative EgtB-IV enzymes, offering insights into the basis for this evolutionary convergence and enhancing our understanding of NHISS active site organization more broadly. The ability to interpret how key residues modulate substrate specificity and regioselectivity has implications for downstream identification of divergent reactivity within the NHISS family. To this end, we identify a previously unclassified clade of OvoA-like enzymes with a seemingly hybrid set of characteristics, suggesting they may represent an evolutionary intermediate between OvoA and EgtB-IV.

非血红素铁依赖性亚砜/硒氧化物合酶(NHISS)是一类独特的金属酶,能够在组氨酸上安装 C-S/Se 键,生成硫代/硒酰亚胺唑类抗氧化剂,如麦角硫因和卵硫醇。这些天然产品对健康的益处日益得到认可。在相关的麦角硫因生物合成酶中,IV 型 EgtBs 脱颖而出,因为它们与其他 EgtB 亚家族的序列相似性较低,这是因为它们最近才从卵硫醇生物合成酶 OvoA 分化而来。在此,我们展示了两种具有代表性的 EgtB-IV 酶的晶体结构,为这种进化趋同的基础提供了见解,并更广泛地加深了我们对 NHISS 活性位点组织的理解。解释关键残基如何调节底物特异性和区域选择性的能力对下游识别 NHISS 家族中的不同反应性具有重要意义。为此,我们发现了一个以前未分类的类似 OvoA 酶的支系,它们具有一系列看似混合的特征,表明它们可能代表了 OvoA 和 EgtB-IV 之间的进化中间体。
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引用次数: 0
Novel, tightly structurally related N-myristoyltransferase inhibitors display equally potent yet distinct inhibitory mechanisms 结构紧密相关的新型 N-肉豆蔻酰基转移酶抑制剂显示出同等效力但不同的抑制机制
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1016/j.str.2024.08.001
Frédéric Rivière, Cyril Dian, Rémi F. Dutheil, Paul Monassa, Carmela Giglione, Thierry Meinnel

N-myristoyltransferases (NMTs) catalyze essential acylations of N-terminal alpha or epsilon amino groups of glycines or lysines. Here, we reveal that peptides tightly fitting the optimal glycine recognition pattern of human NMTs are potent prodrugs relying on a single-turnover mechanism. Sequence scanning of the inhibitory potency of the series closely reflects NMT glycine substrate specificity rules, with the lead inhibitor blocking myristoylation by NMTs of various species. We further redesigned the series based on the recently recognized lysine-myristoylation mechanism by taking advantage of (1) the optimal peptide chassis and (2) lysine side chain mimicry with unnatural enantiomers. Unlike the lead series, the inhibitory properties of the new compounds rely on the protonated state of the side chain amine, which stabilizes a salt bridge with the catalytic base at the active site. Our study provides the basis for designing first-in-class NMT inhibitors tailored for infectious diseases and alternative active site targeting.

N-肉豆蔻酰转移酶(NMTs)可催化甘氨酸或赖氨酸的 N-末端α或ε氨基的必要酰化。在这里,我们揭示了与人类 NMTs 的最佳甘氨酸识别模式紧密配合的多肽是依靠单次转化机制的强效原药。对该系列抑制效力的序列扫描密切反映了 NMT 甘氨酸底物特异性规则,主要抑制剂阻断了不同物种 NMT 的肉豆蔻酰化作用。我们根据最近认识到的赖氨酸-肉豆蔻酰化机制进一步重新设计了该系列,利用了(1)最佳肽底盘和(2)非天然对映体的赖氨酸侧链模拟。与先导系列不同的是,新化合物的抑制特性依赖于侧链胺的质子化状态,这种状态可以稳定活性位点催化碱的盐桥。我们的研究为设计针对传染性疾病和替代活性位点靶向的一流 NMT 抑制剂奠定了基础。
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引用次数: 0
Unveiling the double-edged sword: SOD1 trimers possess tissue-selective toxicity and bind septin-7 in motor neuron-like cells 揭开双刃剑的面纱:SOD1 三聚体具有组织选择性毒性,并能与运动神经元样细胞中的 septin-7 结合
IF 5.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-28 DOI: 10.1016/j.str.2024.08.002
Esther Sue Choi, Brianna Hnath, Congzhou Mike Sha, Nikolay V. Dokholyan

Misfolded species of superoxide dismutase 1 (SOD1) are associated with increased death in amyotrophic lateral sclerosis (ALS) models compared to insoluble protein aggregates. The mechanism by which structurally independent SOD1 trimers cause cellular toxicity is unknown but may drive disease pathology. Here, we uncovered the SOD1 trimer interactome—a map of potential tissue-selective protein-binding partners in the brain, spinal cord, and skeletal muscle. We identified binding partners and key pathways associated with SOD1 trimers and found that trimers may affect normal cellular functions such as dendritic spine morphogenesis and synaptic function in the central nervous system and cellular metabolism in skeletal muscle. We discovered SOD1 trimer-selective enrichment of genes. We performed detailed computational and biochemical characterization of SOD1 trimer protein binding for septin-7. Our investigation highlights key proteins and pathways within distinct tissues, revealing a plausible intersection of genetic and pathophysiological mechanisms in ALS through interactions involving SOD1 trimers.

在肌萎缩性脊髓侧索硬化症(ALS)模型中,与不溶性蛋白聚集体相比,超氧化物歧化酶 1(SOD1)的错误折叠与死亡增加有关。结构独立的 SOD1 三聚体导致细胞毒性的机制尚不清楚,但可能是疾病病理的驱动因素。在这里,我们发现了 SOD1 三聚体相互作用组--大脑、脊髓和骨骼肌中潜在的组织选择性蛋白结合伙伴图谱。我们确定了与 SOD1 三聚体相关的结合伙伴和关键通路,发现三聚体可能会影响正常的细胞功能,如中枢神经系统的树突棘形态发生和突触功能以及骨骼肌的细胞代谢。我们发现了 SOD1 三聚体选择性富集基因。我们对 SOD1 三聚体蛋白与 septin-7 的结合进行了详细的计算和生化鉴定。我们的研究突出了不同组织中的关键蛋白和通路,通过 SOD1 三聚体的相互作用揭示了 ALS 遗传和病理生理机制的合理交叉。
{"title":"Unveiling the double-edged sword: SOD1 trimers possess tissue-selective toxicity and bind septin-7 in motor neuron-like cells","authors":"Esther Sue Choi, Brianna Hnath, Congzhou Mike Sha, Nikolay V. Dokholyan","doi":"10.1016/j.str.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.str.2024.08.002","url":null,"abstract":"<p>Misfolded species of superoxide dismutase 1 (SOD1) are associated with increased death in amyotrophic lateral sclerosis (ALS) models compared to insoluble protein aggregates. The mechanism by which structurally independent SOD1 trimers cause cellular toxicity is unknown but may drive disease pathology. Here, we uncovered the SOD1 trimer interactome—a map of potential tissue-selective protein-binding partners in the brain, spinal cord, and skeletal muscle. We identified binding partners and key pathways associated with SOD1 trimers and found that trimers may affect normal cellular functions such as dendritic spine morphogenesis and synaptic function in the central nervous system and cellular metabolism in skeletal muscle. We discovered SOD1 trimer-selective enrichment of genes. We performed detailed computational and biochemical characterization of SOD1 trimer protein binding for septin-7. Our investigation highlights key proteins and pathways within distinct tissues, revealing a plausible intersection of genetic and pathophysiological mechanisms in ALS through interactions involving SOD1 trimers.</p>","PeriodicalId":22168,"journal":{"name":"Structure","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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