Biochimica et biophysica acta. Molecular cell research最新文献

英文中文

NSUN2 activated by KLF6 can mediate m5C modification of NCOA4 to enhance ferroptosis of OGD/R-induced SH-SY5Y cells in ischemic stroke KLF6激活的NSUN2可介导NCOA4的m5C修饰，增强OGD/ r诱导的缺血性卒中SH-SY5Y细胞的铁凋亡。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-03-01 Epub Date: 2025-12-30 DOI: 10.1016/j.bbamcr.2025.120102

Genshan Gao , Yue Xu , Yao Liu, Shuqing Meng, Nannuan Liu

Ischemic stroke (IS) constitutes the majority of stroke cases. Ferroptosis, a non-apoptotic form of programmed cell death, is an essential mechanism of IS. This study aimed to investigate a ferroptosis-related molecular mechanism in IS progression. IS model in vitro was induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in SH-SY5Y cells. RT-qPCR and Western blotting were performed for detection of NOP2/Sun RNA methyltransferase family member 2 (NSUN2), nuclear receptor coactivator 4 (NCOA4), and Krueppel-like factor 6 (KLF6). Cell functions were assessed by MTT assay, flow cytometry, and enzyme-linked immunosorbent assay. Mitochondrial membrane potential and other ferroptosis indicators were examined using kits. Molecular binding was detected using methylated RNA immunoprecipitation (MeRIP), RIP, dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. IS animal model was established by middle cerebral artery occlusion (MCAO). OGD/R-induced apoptosis, inflammation, and ferroptosis of SH-SY5Y cells were suppressed by NCOA4 knockdown. NSUN2 could promote NCOA4 mRNA stability by mediating 5-methylcytosine (m5C) methylation modification of NCOA4, and YBX1 served as a reader protein. NSUN2 contributed to OGD/R-induced SH-SY5Y cell injury via upregulating NCOA4. KLF6 acted as a transcription factor to activate NSUN2 transcription, and then facilitated nerve injury of OGD/R-induced SH-SY5Y cells. Animal assay showed that silencing NSUN2 inhibited infarct volume, tissue injury, neurological function, and neuroinflammation in MCAO rats. These current findings affirmed that KLF6-activated NSUN2 could contribute to ferroptosis of OGD/R-induced SH-SY5Y cells via inducing NCOA4 m5C modification, providing a novel insight into the mechanism of ferroptosis in IS.

缺血性中风（IS）占中风病例的大多数。铁凋亡是一种非凋亡形式的程序性细胞死亡，是is的重要机制。本研究旨在探讨IS进展中与铁衰相关的分子机制。采用氧-葡萄糖剥夺/再氧化（OGD/R）法诱导SH-SY5Y细胞体外IS模型。采用RT-qPCR和Western blotting检测NOP2/Sun RNA甲基转移酶家族成员2 （NSUN2）、核受体辅助激活因子4 （NCOA4）和krueppel样因子6 （KLF6）。采用MTT法、流式细胞术和酶联免疫吸附法评估细胞功能。采用试剂盒检测线粒体膜电位及其他铁下垂指标。采用甲基化RNA免疫沉淀法（MeRIP）、RIP、双荧光素酶报告基因法和染色质免疫沉淀法（ChIP）检测分子结合。采用大脑中动脉闭塞法（MCAO）建立IS动物模型。下调NCOA4可抑制OGD/ r诱导的SH-SY5Y细胞凋亡、炎症和铁下垂。NSUN2可通过介导NCOA4的5-甲基胞嘧啶（m5C）甲基化修饰，促进NCOA4 mRNA的稳定性，YBX1作为一个读取器蛋白。NSUN2通过上调NCOA4参与OGD/ r诱导的SH-SY5Y细胞损伤。KLF6作为转录因子激活NSUN2转录，进而促进OGD/ r诱导的SH-SY5Y细胞的神经损伤。动物实验表明，沉默NSUN2可抑制MCAO大鼠的梗死体积、组织损伤、神经功能和神经炎症。这些研究结果证实了klf6激活的NSUN2可以通过诱导NCOA4 m5C修饰促进OGD/ r诱导的SH-SY5Y细胞的铁死亡，为IS中铁死亡的机制提供了新的见解。

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引用次数: 0

Prevotella copri leads to colonic barrier dysfunction via the succinate receptor 1-FoxM1-IL-6 axis copri普雷沃氏菌通过琥珀酸受体1-FoxM1-IL-6轴导致结肠屏障功能障碍。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-03-01 Epub Date: 2025-12-30 DOI: 10.1016/j.bbamcr.2025.120099

Rui Li , Shuang Liu , Haiyan Zhang , Xinglin Huang , Wenchu Qian , Daobin Han , Fang Wang , Zhonghui Feng , Tongtong Zhang , Hai Lin , Haifang Li

Prevotella copri, a key commensal bacterium in the human gut microbiome, exhibits both positive and negative abundance correlations with various disorders. Although multiple studies have suggested an association between P. copri and intestinal pathologies, the mechanistic basis remains elusive. In this study, we examined P. copri's effects on colonic physiology in healthy mice, revealing its capacity to compromise intestinal barrier integrity. This was demonstrated through downregulation of colonic tight junction proteins (Occludin and ZO-1) and elevated serum levels of gut permeability markers (LPS and D-LA). We identified succinate as the primary microbial metabolite mediating P. copri's barrier-disrupting effects, with succinate receptor 1 (SUCNR1) being essential for this pathological process. Notably, both P. copri colonization and succinate administration activated the IL-6-STAT3 signaling pathway, leading to transcriptional suppression of the tight junction-related gene, Occludin. Through mechanistic studies, we identified Forkhead box M1 (FoxM1) as a crucial transcription factor regulating P. copri- or succinate-induced Il-6 expression. Clinical relevance was established through human cohort analyses showing significant positive correlations between fecal succinate levels and plasma markers of gut permeability. These findings elucidate a novel mechanistic pathway through which P. copri impairs colonic function, suggesting therapeutic potential in colitis through strategies targeting either P. copri abundance or microbial succinate production.

copri普雷沃特菌是人类肠道微生物群中的一种重要的共生细菌，其丰度与多种疾病呈正相关和负相关。尽管多项研究表明copri与肠道病变之间存在关联，但其机制基础仍难以捉摸。在这项研究中，我们检测了copri对健康小鼠结肠生理的影响，揭示了其损害肠道屏障完整性的能力。这可以通过结肠紧密连接蛋白（Occludin和ZO-1）的下调和肠道通透性标志物（LPS和D-LA）的血清水平升高来证明。我们发现琥珀酸盐是介导copri屏障破坏作用的主要微生物代谢物，琥珀酸受体1 （SUCNR1）在这一病理过程中至关重要。值得注意的是，copri定植和琥珀酸盐给药都激活了IL-6-STAT3信号通路，导致紧密连接相关基因Occludin的转录抑制。通过机制研究，我们确定叉头盒M1 （FoxM1）是调节P. copri或琥珀酸诱导的Il-6表达的关键转录因子。通过人类队列分析，建立了临床相关性，显示粪便琥珀酸盐水平与肠道通透性血浆标志物之间存在显著的正相关。这些发现阐明了copri损害结肠功能的一种新的机制途径，提示通过针对copri丰度或微生物琥珀酸盐产生的策略治疗结肠炎的潜力。

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引用次数: 0

SPRED2 controls the severity of cisplatin-induced acute kidney injury by inhibiting ERK activation and TNFα production in mice SPRED2通过抑制小鼠ERK活化和TNFα产生来控制顺铂诱导的急性肾损伤的严重程度

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-11-30 DOI: 10.1016/j.bbamcr.2025.120091

Xu Yang , Jiali He , Tong Gao , Masayoshi Fujisawa , Toshiaki Ohara , Steven L. Kunkel , Teizo Yoshimura , Akihiro Matsukawa

Cisplatin is an effective chemotherapeutic agent used to treat solid tumors, but its clinical use is limited by acute kidney injury (AKI), in which ERK signaling plays a crucial role. Here, we investigated whether Sprouty-related EVH1 domain-containing protein 2 (SPRED2), an endogenous inhibitor of the Ras/Raf/ERK pathway, protects against cisplatin-induced AKI. Spred2^−/− mice showed more severe renal injury and stronger ERK activation than wild-type (WT) mice, whereas pretreatment with the MEK inhibitor U0126 markedly attenuated the injury. In HK-2 cells (proximal tubular cells), SPRED2 knockdown enhanced cisplatin-induced apoptosis and caspase-3 activation, accompanied by decreased Bcl-2 expression. Spred2^−/− kidneys displayed increased macrophage infiltration and elevated Tnfα, Il1b, and Ccl2 expression. Neutralization of TNFα with anti-TNFα antibody ameliorated renal injury and reduced the levels of Il1b and Ccl2 mRNA in Spred2^−/− mice. In vitro, TNFα slightly decreased the viability of control and SPRED2 knockdown HK-2 cells without cisplatin treatment, but the decreased viability was augmented in SPRED2 knockdown cells by cisplatin. Immunohistochemistry revealed that macrophages were the predominant TNFα-positive cell population. Bone marrow–derived macrophages from Spred2^−/− mice produced higher levels of TNFα in response to cisplatin compared with control cells, and this increase was markedly suppressed by U0126.

These findings indicate that endogenous SPRED2 protects kidneys from cisplatin-induced AKI by limiting ERK activation, tubular apoptosis, and TNFα-mediated inflammation.

顺铂是一种用于治疗实体瘤的有效化疗药物，但其临床应用受到急性肾损伤（AKI）的限制，其中ERK信号在其中起着至关重要的作用。在这里，我们研究了sprouty相关的EVH1结构域蛋白2 (SPRED2)，一种Ras/Raf/ERK途径的内源性抑制剂，是否对顺铂诱导的AKI有保护作用。与野生型（WT）小鼠相比，Spred2−/−小鼠表现出更严重的肾损伤和更强的ERK激活，而MEK抑制剂U0126预处理可显著减轻损伤。在HK-2细胞（近端小管细胞）中，SPRED2敲低可增强顺铂诱导的凋亡和caspase-3激活，并伴有Bcl-2表达降低。Spred2−/−肾脏显示巨噬细胞浸润增加，Tnfα、Il1b和Ccl2表达升高。用抗tnf - α抗体中和tnf - α可改善Spred2−/−小鼠的肾损伤，并降低il - 1b和Ccl2 mRNA的水平。体外实验中，未经顺铂治疗的对照组和SPRED2敲低的HK-2细胞的活力略有下降，但在SPRED2敲低的细胞中，顺铂增强了这种下降的活力。免疫组化结果显示，tnf α阳性细胞群以巨噬细胞为主。与对照细胞相比，Spred2 - / -小鼠骨髓源性巨噬细胞对顺铂产生更高水平的tnf - α，而U0126明显抑制了这种增加。这些发现表明，内源性SPRED2通过限制ERK激活、肾小管凋亡和tnf α介导的炎症，保护肾脏免受顺铂诱导的AKI。

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引用次数: 0

Assessing the involvement of tumor-secreted factors in the inhibition of muscle differentiation 评估肿瘤分泌因子在肌肉分化抑制中的作用

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-12-04 DOI: 10.1016/j.bbamcr.2025.120093

Miranda van der Ende , Xiaolin Li , Mieke Poland , Fleur Jansen , Jocelijn Meijerink , Jaap Keijer , Renger F. Witkamp , Sander Grefte , Klaske van Norren

Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, predominantly caused by muscle wasting. While tumors can elicit detrimental effects on skeletal muscle function, the contribution of specific tumor-derived mediators remains elusive. To explore this, we investigated the impact of conditioned media (CM) from four cachexia-inducing tumor cell lines (KPC, 4662, LLC, and C26) on muscle differentiation using C2C12 cells. Creatine kinase (CK) activity was measured as an indicator of muscle wasting, and global gene expression changes in C2C12 cells were analyzed via RNA sequencing. Cytokine profiling of the CM identified 111 immune factors, and mimic combinations of the most abundant cytokines from KPC CM were tested for their effects on CK activity. Additionally, the involvement of tumor-derived PGE2 was assessed via CRISPR/Cas9-mediated knockout of the Ptgs2 gene in KPC cells. CM from all tumor cell lines significantly reduced CK activity in C2C12 cells, consistent with downregulation of CKm gene expression. Global gene expression profiles revealed upregulation of immune-related pathways in C2C12 cells exposed to KPC CM. However, mixtures of the 14 most abundant cytokines in CM had minimal effects on CK activity, and tumor-derived PGE2 showed no significant effect on CK activity or muscle cell differentiation. These findings suggest that the observed muscle-wasting effects of cachexia-inducing tumor cells cannot be replicated by the most abundant cytokines present in CM alone, highlighting the need for further research to identify the key tumor-derived factors responsible for cancer-induced muscle wasting.

癌症恶病质是一种多因素综合征，以不自主和病理性体重减轻为特征，主要由肌肉萎缩引起。虽然肿瘤可引起对骨骼肌功能的有害影响，但特异性肿瘤衍生介质的贡献仍然难以捉摸。为了探讨这一点，我们研究了来自四种恶病质诱导肿瘤细胞系（KPC、4662、LLC和C26）的条件培养基（CM）对C2C12细胞肌肉分化的影响。测定肌酸激酶（CK）活性作为肌肉萎缩的指标，并通过RNA测序分析C2C12细胞整体基因表达变化。细胞因子分析鉴定了111个免疫因子，并测试了KPC CM中最丰富的细胞因子模拟组合对CK活性的影响。此外，通过CRISPR/ cas9介导的敲除KPC细胞中的Ptgs2基因来评估肿瘤源性PGE2的参与。所有肿瘤细胞系的CM均显著降低C2C12细胞的CK活性，与CKm基因表达下调一致。全球基因表达谱显示，暴露于KPC CM的C2C12细胞中免疫相关通路上调。然而，CM中14种最丰富的细胞因子的混合物对CK活性的影响很小，肿瘤来源的PGE2对CK活性或肌肉细胞分化没有显著影响。这些发现表明，观察到的恶病质诱导肿瘤细胞的肌肉萎缩效应不能被CM中最丰富的细胞因子所复制，这突出了进一步研究确定癌症诱导肌肉萎缩的关键肿瘤来源因素的必要性。

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引用次数: 0

Metabolic reprogramming is implicated in the differential response of the CAL-1 plasmacytoid dendritic cell line to autophagy inhibitors 代谢重编程涉及CAL-1浆细胞样树突状细胞系对自噬抑制剂的差异反应。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-11-27 DOI: 10.1016/j.bbamcr.2025.120090

Carlota Ramalhinho , Paulo Antas , Philippe Pierre , Iola F. Duarte , Catarina R. Almeida

Plasmacytoid dendritic cells (pDCs) produce large amounts of type I Interferons (IFN) and pro-inflammatory cytokines, playing crucial roles in antiviral and anticancer immunity as well as in autoimmune diseases. Understanding the mechanisms that regulate pDC function is therefore essential. Autophagy, a process responsible for recycling intracellular components, influences cellular metabolism and modulates immune responses. Here, we used the human CAL-1 pDC cell line, a validated model for primary pDCs, to investigate the functional impact of autophagy inhibition and the contribution of metabolism to these effects. CAL-1 cells were treated with two autophagy inhibitors, Spautin-1 and VPS34-IN1, and cytokine production was assessed by RT-qPCR and ELISA, while cellular metabolism was analysed by untargeted metabolomics of cell extracts and of medium supernatants. VPS34-IN1, but not Spautin-1, induced robust expression of IFN-β and TNF-α. The two inhibitors also elicited distinct metabolic responses: Spautin-1 enhanced glycolysis, promoted an anabolic phenotype with increased utilization of amino acids, and upregulated mTOR signaling. In contrast, VPS34-IN1 decreased glycolysis, increased intracellular amino acids, reduced TCA intermediates, and induced energy stress, reflected by an increased AMP/(ADP + ATP) ratio and decreased NAD⁺. These changes were consistent with AMPK activation, and pharmacological inhibition of AMPK with dorsomorphin (compound C) abolished cytokine production in VPS34-IN1-treated cells. Together, these results indicate that differential cytokine responses to autophagy inhibition are driven primarily by metabolic rewiring rather than autophagic flux per se, highlighting the interplay between metabolism, mitochondrial ROS, and signaling pathways in pDC activation.

浆细胞样树突状细胞（pDCs）产生大量I型干扰素（IFN）和促炎细胞因子，在抗病毒和抗癌免疫以及自身免疫性疾病中起着至关重要的作用。因此，了解调控pDC功能的机制至关重要。自噬是一种负责细胞内成分循环的过程，影响细胞代谢并调节免疫反应。在这里，我们使用人CAL-1 pDC细胞系（一种验证过的原代pDC模型）来研究自噬抑制对功能的影响以及代谢对这些影响的贡献。用两种自噬抑制剂Spautin-1和VPS34-IN1处理CAL-1细胞，通过RT-qPCR和ELISA检测细胞因子的产生，通过细胞提取物和培养基上清液的非靶向代谢组学分析细胞代谢。VPS34-IN1诱导IFN-β和TNF-α的强烈表达，而Spautin-1不诱导。这两种抑制剂也引发了不同的代谢反应：Spautin-1增强糖酵解，促进合成代谢表型，增加氨基酸的利用，上调mTOR信号。相反，VPS34-IN1降低糖酵解，增加细胞内氨基酸，减少TCA中间体，诱导能量应激，表现为AMP/（ADP + ATP）比值升高和NAD+降低。这些变化与AMPK的激活一致，用dorsomorphin（化合物C）抑制AMPK可消除vps34 - in1处理的细胞中细胞因子的产生。总之，这些结果表明，细胞因子对自噬抑制的差异反应主要是由代谢重布线驱动的，而不是自噬通量本身，这突出了代谢、线粒体ROS和pDC激活信号通路之间的相互作用。

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引用次数: 0

Corrigendum to “A fluorescent protein C-terminal fusion knock-in is functional with TRPA1 but not TRPC5” [Biochim. Biophys. Acta Mol. Cell Res. 1872(2) (2025) 119887] “一种荧光蛋白c端融合敲入对TRPA1起作用，但对TRPC5不起作用”的更正[biochem]。Biophys。分子细胞学报，1872(2)(2025)[19887]。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-08-15 DOI: 10.1016/j.bbamcr.2025.120042

Aaron Tragl , Alexandra Ptakova , Viktor Sinica , Rathej Meerupally , Christine König , Carolina Roza , Ivan Barvík , Viktorie Vlachova , Katharina Zimmermann

引用次数: 0

Corrigendum to “Protein synthesis inhibition promotes nitric oxide generation and activation of CGKII-dependent downstream signaling pathways in the retina” [Biochim. Biophys. Acta (BBA) Mol. Cell Res. 1867 (2020) 118732 10.1016/j.bbamcr.2020.118732] “蛋白质合成抑制促进一氧化氮的产生和视网膜中cgkii依赖的下游信号通路的激活”[biochem]的更正。Biophys。[j].中国生物医学工程学报，2016,32(1):1 - 2。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-09-01 DOI: 10.1016/j.bbamcr.2025.120050

Marcelo Cossenza , Renato Socodato , Telmo A. Mejía-García , Ivan Domith , Camila C. Portugal , Luis F.H. Gladulich , Aline T. Duarte-Silva , Latika Khatri , Shannon Antoine , Franz Hofmann , Edward B. Ziff , Roberto Paes-de-Carvalho

引用次数: 0

Corrigendum to “Inhibition of autophagy sensitises cells to hydrogen peroxide-induced apoptosis: Protective effect of mild thermotolerance acquired at 40 °C” [Biochim. Biophys. Acta Mol. Cell Res. (2016) volume 1863(12) 3050-3064 / PMID: 27666506] “抑制自噬使细胞对过氧化氢诱导的凋亡敏感：在40°C下获得的轻度耐热性的保护作用”[biochem]的更正。Biophys。Acta Mol Cell Res. (2016) volume 1863(12) 3050-3064 / PMID: 27666506]。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-09-19 DOI: 10.1016/j.bbamcr.2025.120061

M. Redza-Dutordoir, S. Kassis, H. Ve, M. Grondin, D.A. Averill-Bates

引用次数: 0

Corrigendum to “Activation of ER stress and apoptosis by hydrogen peroxide in HeLa cells: Protective role of mild heat preconditioning at 40 °C” [Biochim. Biophys. Acta Mol. Cell Res., 1813 (2011) 1987–1999. / PMID: 21875624] “过氧化氢在HeLa细胞中内质网应激和凋亡的激活：40°C轻度热预处理的保护作用”的更正[biochem]。Biophys。分子细胞学报，1813(2011)1987-1999。/ pmid: 21875624]。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-11-12 DOI: 10.1016/j.bbamcr.2025.120084

Pragathi Pallepati, Diana A. Averill-Bates

引用次数: 0

Structural diversity of full-length human αvβ3 integrin revealed by cryo-EM 低温电镜分析人αvβ3整联素的结构多样性。

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research

Pub Date : 2026-02-01 Epub Date: 2025-11-29 DOI: 10.1016/j.bbamcr.2025.120089

Cang Wu , Yuanzhu Gao , Weiyan Wang , Zhoufang Li , Qing Shu , Xi Zhang

Integrins are essential transmembrane receptors that orchestrate cell adhesion, migration, and survival, and have emerged as promising therapeutic targets for cancer, fibrosis, and autoimmune diseases. However, most integrin-targeted drugs have failed in clinical trials due to limited efficacy and unexpected off-target effects, reflecting an incomplete understanding of integrin conformational regulation. Here, we present a series of high-resolution cryo-EM structures of human integrin αvβ3 in both apo and ligand-bound states by collecting a large amount of data. Consequently, we resolved six conformations of integrin in the apo state, five of which were previously uncharacterized, along with five distinct ligand-bound states, thereby revealing a continuum of conformational transitions underlying integrin activation. Notably, CWHM-12 enables the simultaneous coexistence of integrin in closing and opening inhibited states, revealing a mechanism that differs fundamentally from that of conventional RGD peptide-based inhibitors. Then, our study provides a structural framework for understanding integrin activation diversity and lays the foundation for rational design of next-generation inhibitors with improved precision and reduced off-target effects.

整合素是协调细胞粘附、迁移和存活的重要跨膜受体，已成为癌症、纤维化和自身免疫性疾病的有希望的治疗靶点。然而，大多数整合素靶向药物由于疗效有限和意想不到的脱靶效应而在临床试验中失败，反映了对整合素构象调控的不完全理解。在此，我们通过收集大量数据，获得了一系列载脂蛋白和配体结合态的人整合素αvβ3的高分辨率冷冻电镜结构。因此，我们在载脂蛋白状态下解析了整合素的六种构象，其中五种以前未被表征，以及五种不同的配体结合状态，从而揭示了整合素激活下的连续构象转变。值得注意的是，CWHM-12使整合素同时处于关闭和打开抑制状态，揭示了一种与传统RGD肽抑制剂根本不同的机制。因此，我们的研究为理解整合素激活多样性提供了一个结构框架，并为合理设计具有更高精度和减少脱靶效应的下一代抑制剂奠定了基础。

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引用次数: 0

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