Direct visualization of the conformational dynamics of single influenza hemagglutinin trimers

• Dibyendu Kumar Das ^[1] ; Ramesh Govindan ^[1] ; Ivana Nikić-Spiegel ^[2]
  1. [1] Tufts University

     Tufts University

     City of Medford, Estados Unidos

     
  2. [2] University of Tuebingen
• Localización: Cell, ISSN 0092-8674, Vol. 174, Nº. 4, 2018, págs. 926-937
• Idioma: inglés
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• Resumen

  • 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, using single-molecule Förster resonance energy transfer (smFRET)-imaging, we directly visualized 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.