Crystal structure of the pre-fusion Nipah virus fusion glycoprotein reveals a novel hexamer-of-trimers assembly Journal Article
| Authors: | Xu, K.; Chan, Y. P.; Bradel-Tretheway, B.; Akyol-Ataman, Z.; Zhu, Y.; Dutta, S.; Yan, L.; Feng, Y.; Wang, L. F.; Skiniotis, G.; Lee, B.; Zhou, Z. H.; Broder, C. C.; Aguilar, H. C.; Nikolov, D. B. |
| Article Title: | Crystal structure of the pre-fusion Nipah virus fusion glycoprotein reveals a novel hexamer-of-trimers assembly |
| Abstract: | Nipah virus (NiV) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. The G glycoprotein attaches to cell receptors, triggering the fusion (F) glycoprotein to execute membrane fusion. Here we report the first crystal structure of the pre-fusion form of the NiV-F glycoprotein ectodomain. Interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. Electron tomography of Nipah virus-like particles supported the hexameric pre-fusion model, and biochemical analyses supported the hexamer-of-trimers F assembly in solution. Importantly, structure-assisted site-directed mutagenesis of the interfaces between F trimers highlighted the functional relevance of the hexameric assembly. Shown here, in both cell-cell fusion and virus-cell fusion systems, our results suggested that this hexamer-of-trimers assembly was important during fusion pore formation. We propose that this assembly would stabilize the pre-fusion F conformation prior to cell attachment and facilitate the coordinated transition to a post-fusion conformation of all six F trimers upon triggering of a single trimer. Together, our data reveal a novel and functional pre-fusion architecture of a paramyxoviral fusion glycoprotein. © 2015, Public Library of Science, All Rights Reserved. |
| Keywords: | protein expression; nonhuman; flow cytometry; protein conformation; animal cell; protein assembly; hybrid protein; crystal structure; real time polymerase chain reaction; x ray crystallography; polyacrylamide gel electrophoresis; transmission electron microscopy; affinity chromatography; size exclusion chromatography; nipah virus; article; electron tomography |
| Journal Title: | PLoS Pathogens |
| Volume: | 11 |
| Issue: | 12 |
| ISSN: | 1553-7366 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-12-08 |
| Start Page: | e1005322 |
| Language: | English |
| DOI: | 10.1371/journal.ppat.1005322 |
| PROVIDER: | scopus |
| PMCID: | PMC4672880 |
| PUBMED: | 26646856 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
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