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dc.contributor.authorLin, Xingcheng
Noel, Jeffrey K.
Wang, Qinghua
Ma, Jianpeng
Onuchic, José N.
dc.date.accessioned 2017-05-19T19:09:39Z
dc.date.available 2017-05-19T19:09:39Z
dc.date.issued 2016
dc.identifier.citation Lin, Xingcheng, Noel, Jeffrey K., Wang, Qinghua, et al.. "Lowered pH Leads to Fusion Peptide Release and a Highly Dynamic Intermediate of Influenza Hemagglutinin." The Journal of Physical Chemistry B, 120, no. 36 (2016) American Chemical Society: 9654-9660. https://doi.org/10.1021/acs.jpcb.6b06775.
dc.identifier.urihttps://hdl.handle.net/1911/94291
dc.description.abstract Hemagglutinin (HA), the membrane-bound fusion protein of the influenza virus, enables the entry of virus into host cells via a structural rearrangement. There is strong evidence that the primary trigger for this rearrangement is the low pH environment of a late endosome. To understand the structural basis and the dynamic consequences of the pH trigger, we employed explicit-solvent molecular dynamics simulations to investigate the initial stages of the HA transition. Our results indicate that lowered pH destabilizes HA and speeds up the dissociation of the fusion peptides (FPs). A buried salt bridge between the N-terminus and Asp1122 of HA stem domain locks the FPs and may act as one of the pH sensors. In line with recent observations from simplified protein models, we find that, after the dissociation of FPs, a structural order–disorder transition in a loop connecting the central coiled-coil to the C-terminal domains produces a highly mobile HA. This motion suggests the existence of a long-lived asymmetric or “symmetry-broken” intermediate during the HA conformational change. This intermediate conformation is consistent with models of hemifusion, and its early formation during the conformational change has implications for the aggregation seen in HA activity.
dc.language.iso eng
dc.publisher American Chemical Society
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society.
dc.title Lowered pH Leads to Fusion Peptide Release and a Highly Dynamic Intermediate of Influenza Hemagglutinin
dc.type Journal article
dc.citation.journalTitle The Journal of Physical Chemistry B
dc.contributor.org Center for Theoretical Biological Physics
dc.citation.volumeNumber 120
dc.citation.issueNumber 36
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1021/acs.jpcb.6b06775
dc.identifier.pmcid PMC5130312
dc.identifier.pmid 27541202
dc.type.publication post-print
dc.citation.firstpage 9654
dc.citation.lastpage 9660


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