Zernike Institute for Advanced Materials, University of Groningen, 9747 AG Groningen, The Netherlands; email:
School of Chemistry; Faculty of Science, Medicine and Health; University of Wollongong, Wollongong, New South Wales 2522, Australia; email:
Annu Rev Biophys. 2018 May 20;47:153-173. doi: 10.1146/annurev-biophys-070317-033018. Epub 2018 Mar 1.
Influenza hemagglutinin (HA) is a viral membrane protein responsible for the initial steps of the entry of influenza virus into the host cell. It mediates binding of the virus particle to the host-cell membrane and catalyzes fusion of the viral membrane with that of the host. HA is therefore a major target in the development of antiviral strategies. The fusion of two membranes involves high activation barriers and proceeds through several intermediate states. Here, we provide a biophysical description of the membrane fusion process, relating its kinetic and thermodynamic properties to the large conformational changes taking place in HA and placing these in the context of multiple HA proteins working together to mediate fusion. Furthermore, we highlight the role of novel single-particle experiments and computational approaches in understanding the fusion process and their complementarity with other biophysical approaches.
流感血凝素（HA）是一种病毒膜蛋白，负责流感病毒进入宿主细胞的初始步骤。它介导病毒颗粒与宿主细胞膜的结合，并催化病毒膜与宿主膜的融合。因此，HA 是抗病毒策略开发的主要目标。两个膜的融合涉及高激活障碍，并通过几个中间状态进行。在这里，我们提供了一个关于膜融合过程的生物物理描述，将其动力学和热力学性质与 HA 中发生的大构象变化联系起来，并将其置于多个 HA 蛋白共同作用以介导融合的背景下。此外，我们强调了新型单颗粒实验和计算方法在理解融合过程中的作用，以及它们与其他生物物理方法的互补性。
