The nanoscale organization of the Nipah virus fusion protein informs new membrane fusion mechanisms

• DOI: 10.7554/elife.97017.2
• Publication Date: 2024-11-08T11:25:14Z
• Authors: Qian Wang; Jinxin Liu; Yuhang Luo; Vicky Kliemke; Giuliana Leonarda...; Jingjing Wang; Qian Liu
• Keywords: paramyxovirus; QH301-705.5; Biochemistry and Chemical Biology; Science; membrane fusion; Q; R; Medicine; Biology (General); single-molecule localization microscopy

Paramyxovirus membrane fusion requires an attachment protein for receptor binding and a triggering. Nipah virus (NiV) (G) binds to ephrinB2 or -B3 receptors, (F) mediates fusion. NiV-F is class I activated by endosomal cleavage. The crystal structure of soluble GCN4-decorated shows hexamer-of-trimer assembly. Here, we used single-molecule localization microscopy quantify the distribution organization on cell virus-like-particle membranes at nanometer precision. We found that biological forms distinctive clusters are independent cleavage expression levels. sequestration into dense favors nano-distribution susceptible mutations interface, putative oligomerization motif transmembrane domain. also show nanoclusters maintained NiV-F-AP-2 interactions clathrin coat propose facilitates triggering mixed population molecules with varied degrees opportunities interacting NiV-G/receptor complex. These observations provide insights in-situ activation mechanisms NiV machinery.