tetano
Editor, Senior Moderator
Cell. 2018 Jun 21. pii: S0092-8674(18)30713-X. doi: 10.1016/j.cell.2018.05.050. [Epub ahead of print]
[h=1]Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers.[/h] Das DK[SUP]1[/SUP], Govindan R[SUP]2[/SUP], Nikić-Spiegel I[SUP]3[/SUP], Krammer F[SUP]4[/SUP], Lemke EA[SUP]5[/SUP], Munro JB[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 F?rster 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.
[h=4]KEYWORDS:[/h] membrane fusion; protein dynamics; single-molecule fluorescence; smFRET; virus entry
PMID: 29961575 DOI: 10.1016/j.cell.2018.05.050
[h=1]Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers.[/h] Das DK[SUP]1[/SUP], Govindan R[SUP]2[/SUP], Nikić-Spiegel I[SUP]3[/SUP], Krammer F[SUP]4[/SUP], Lemke EA[SUP]5[/SUP], Munro JB[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 F?rster 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.
[h=4]KEYWORDS:[/h] membrane fusion; protein dynamics; single-molecule fluorescence; smFRET; virus entry
PMID: 29961575 DOI: 10.1016/j.cell.2018.05.050