Lee Kelly K
Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
QRB Discov. 2025 Mar 31;6:e14. doi: 10.1017/qrd.2025.3. eCollection 2025.
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.
病毒是高度动态的大分子组装体。从病毒粒子组装到成熟、受体对接、细胞进入、脱壳和基因组递送，它们在感染周期的几乎每个阶段都会经历结构和组织的大规模变化。了解病毒感染周期中的结构转变和动力学是一个广阔的研究领域，这也有助于深入了解阻断感染、复制和传播的机制。此外，病毒所执行的过程是类似细胞过程的优秀模型系统，但形式更易于研究。由于组装体的大小和复杂性以及所占据功能状态的异质性和短暂性，捕获和分析这些动态事件对许多结构生物学方法构成了重大挑战。在这里，我们研究蛋白质介导的膜融合过程，该过程由包膜病毒表面的专门机制执行，导致病毒基因组的递送。冷冻电子断层扫描和结构质谱这两种互补方法的应用，能够对完整融合系统中的动态中间状态进行成像和探测，从而为驱动这一基本生物学过程的机制和机制提供新的理解。
