Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
Department of Medicinal Chemistry, University of Washington, Seattle, WA, USA; Biological Structure Physics and Design Graduate Program, University of Washington, Seattle, WA, USA.
Trends Biochem Sci. 2024 Oct;49(10):916-931. doi: 10.1016/j.tibs.2024.06.012. Epub 2024 Jul 24.
Protein-mediated membrane fusion is the dynamic process where specialized protein machinery undergoes dramatic conformational changes that drive two membrane bilayers together, leading to lipid mixing and opening of a fusion pore between previously separate membrane-bound compartments. Membrane fusion is an essential stage of enveloped virus entry that results in viral genome delivery into host cells. Recent studies applying cryo-electron microscopy techniques in a time-resolved fashion provide unprecedented glimpses into the interaction of viral fusion proteins and membranes, revealing fusion intermediate states from the initiation of fusion to release of the viral genome. In combination with complementary structural, biophysical, and computation modeling approaches, these advances are shedding new light on the mechanics and dynamics of protein-mediated membrane fusion.
蛋白介导的膜融合是一种动态过程，在此过程中，专门的蛋白机制经历剧烈的构象变化，促使两个膜双层靠拢，导致脂质混合，并在先前分隔的膜结合隔室之间打开融合孔。膜融合是包膜病毒进入的一个重要阶段，导致病毒基因组递送到宿主细胞中。最近应用低温电子显微镜技术进行时分辨研究提供了前所未有的包膜病毒融合蛋白和膜相互作用的视角，揭示了融合起始到病毒基因组释放过程中的融合中间状态。与互补的结构、生物物理和计算建模方法相结合，这些进展为蛋白介导的膜融合的力学和动力学提供了新的认识。
