EphrinB2 clustering by Nipah virus G is required to activate and trap F intermediates at supported lipid bilayer-cell interfaces.

Autor: Wong JJ; Department of Structural Biology, Stanford University, Stanford, CA, USA., Chen Z; Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, China.; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA., Chung JK; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA., Groves JT; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA. jtgroves@lbl.gov tjardetz@stanford.edu., Jardetzky TS; Department of Structural Biology, Stanford University, Stanford, CA, USA. jtgroves@lbl.gov tjardetz@stanford.edu.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2021 Jan 27; Vol. 7 (5). Date of Electronic Publication: 2021 Jan 27 (Print Publication: 2021).
DOI: 10.1126/sciadv.abe1235
Abstrakt: Paramyxovirus membrane fusion requires an attachment protein that binds to a host cell receptor and a fusion protein that merges the viral and host membranes. For Nipah virus (NiV), the G attachment protein binds ephrinB2/B3 receptors and activates F-mediated fusion. To visualize dynamic events of these proteins at the membrane interface, we reconstituted NiV fusion activation by overlaying F- and G-expressing cells onto ephrinB2-functionalized supported lipid bilayers and used TIRF microscopy to follow F, G, and ephrinB2. We found that G and ephrinB2 form clusters and that oligomerization of ephrinB2 is necessary for F activation. Single-molecule tracking of F particles revealed accumulation of an immobilized intermediate upon activation. We found no evidence for stable F-G protein complexes before or after activation. These observations lead to a revised model for NiV fusion activation and provide a foundation for investigating other multicomponent viral fusion systems.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze: MEDLINE