Article
Capture and Imaging of a Prehairpin Fusion Intermediate of the Paramyxovirus PIV5
Proceedings of the National Academy of Sciences of the United States of America
(2011)
Abstract
During cell entry, enveloped viruses fuse their viral membrane with a cellular membrane in a process driven by energetically favorable, large-scale conformational rearrangements of their fusion proteins. Structures of the pre- and postfusion states of the fusion proteins including paramyxovirus PIV5 F and influenza virus hemagglutinin suggest that this occurs via two intermediates. Following formation of an initial complex, the proteins structurally elongate, driving a hydrophobic N-terminal "fusion peptide" away from the protein surface into the target membrane. Paradoxically, this first conformation change moves the viral and cellular bilayers further apart. Next, the fusion proteins form a hairpin that drives the two membranes into close opposition.While the pre- and post-fusion hairpin forms have been characterized crystallographically, the transiently extended prehairpin intermediate has not been visualized. To provide evidence for this extended intermediate we measured the interbilayer spacing of a paramyxovirus trapped in the process of fusing with solid-supported bilayers. A gold-labeled peptide that binds the prehairpin intermediate was used to stabilize and specifically image F-proteins in the prehairpin intermediate. The interbilayer spacing is precisely that predicted from a computational model of the prehairpin, providing strong evidence for its structure and functional role. Moreover, the F-proteins in the prehairpin conformation preferentially localize to a patch between the target and viral membranes, consistent with the fact that the formation of the prehairpin is triggered by local contacts between F- and neighboring viral receptor-binding proteins (HN) only when HN binds lipids in its target membrane.
Keywords
- Hemagglutinins,
- Neuraminidase,
- Human parainfluenza
Disciplines
Publication Date
December 27, 2011
DOI
10.1073/pnas.1116034108
Citation Information
Alexander Y. Fadeev, Yong-ho Kim, Jason E. Donald, Gevorg S. Grigoryan, et al.. "Capture and Imaging of a Prehairpin Fusion Intermediate of the Paramyxovirus PIV5" Proceedings of the National Academy of Sciences of the United States of America Vol. 108 Iss. 52 (2011) p. 20992 - 20997 Available at: http://works.bepress.com/alexander_fadeev/12/