Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers

作者：Das Dibyendu Kumar^*; Govindan Ramesh; Nikic Spiegel Ivana; Krammer Florian; Lemke Edward A; Munro James B^*

来源：Cell, 2018, 174(4): 926-+.

DOI：10.1016/j.cell.2018.05.050

Influenza hemagglutinin (HA) is the canonical type I viral envelope glycoprotein and provides a template for the membrane-fusion mechanisms of numerous viruses. The current model of HA-mediated membrane fusion describes a static "spring-loaded" fusion domain (HA2) at neutral pH. Acidic pH triggers a singular irreversible conformational rearrangement in HA2 that fuses viral and cellular membranes. Here, pH-triggered conformational changes of HA trimers on the viral surface. Our analyses reveal reversible exchange between the pre-fusion and two intermediate conformations of HA2. Acidification of pH and receptor binding shifts the dynamic equilibrium of HA2 in favor of forward progression along the membrane-fusion reaction coordinate. Interaction with the target membrane promotes irreversible transition of HA2 to the post-fusion state. The reversibility of HA2 conformation may protect against transition to the post-fusion state prior to arrival at the target membrane.

• 出版日期2018-8-9