Unleashing virus structural biology: Probing protein and membrane intermediates in the dynamic process of membrane fusion.

Q3 Biochemistry, Genetics and Molecular Biology
QRB Discovery Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI:10.1017/qrd.2025.3
Kelly K Lee
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引用次数: 0

Abstract

Viruses are highly dynamic macromolecular assemblies. They undergo large-scale changes in structure and organization at nearly every stage of their infectious cycles from virion assembly to maturation, receptor docking, cell entry, uncoating and genome delivery. Understanding structural transformations and dynamics across the virus infectious cycle is an expansive area for research that that can also provide insight into mechanisms for blocking infection, replication, and transmission. Additionally, the processes viruses carry out serve as excellent model systems for analogous cellular processes, but in more accessible form. Capturing and analyzing these dynamic events poses a major challenge for many structural biological approaches due to the size and complexity of the assemblies and the heterogeneity and transience of the functional states that are populated. Here we examine the process of protein-mediated membrane fusion, which is carried out by specialized machinery on enveloped virus surfaces leading to delivery of the viral genome. Application of two complementary methods, cryo-electron tomography and structural mass spectrometry enable dynamic intermediate states in intact fusion systems to be imaged and probed, providing a new understanding of the mechanisms and machinery that drive this fundamental biological process.

释放病毒结构生物学:探索膜融合动态过程中的蛋白质和膜中间体。
病毒是高度动态的大分子集合。从病毒粒子组装到成熟、受体对接、细胞进入、脱包膜和基因组传递,它们在感染周期的几乎每个阶段都经历了大规模的结构和组织变化。了解整个病毒感染周期的结构转变和动力学是一个广阔的研究领域,也可以为阻断感染、复制和传播的机制提供见解。此外,病毒进行的过程是类似细胞过程的优秀模型系统,但以更容易获得的形式。捕获和分析这些动态事件对许多结构生物学方法提出了重大挑战,因为组装的大小和复杂性以及所填充的功能状态的异质性和短暂性。在这里,我们研究了蛋白质介导的膜融合过程,这是由包膜病毒表面的专门机器进行的,导致病毒基因组的传递。低温电子断层扫描和结构质谱两种互补方法的应用,使完整融合系统中的动态中间状态得以成像和探测,为驱动这一基本生物过程的机制和机制提供了新的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
QRB Discovery
QRB Discovery Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
3.60
自引率
0.00%
发文量
18
审稿时长
12 weeks
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