Structure of a lipid-bound viral membrane assembly protein reveals a modality for enclosing the lipid bilayer

Prabhat Kumar Pathak, Shuxia Peng, Xiangzhi Meng, Yue Han, Bing Zhang, Fushun Zhang, Yan Xiang, Junpeng Deng

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Cellular membranes are maintained as closed compartments, broken up only transiently during membrane reorganization or lipid transportation. However, open-ended membranes, likely derived from scissions of the endoplasmic reticulum, persist in vaccinia virus-infected cells during the assembly of the viral envelope. A group of viral membrane assembly proteins (VMAPs) were identified as essential for this process. To understand the mechanism of VMAPs, we determined the 2.2-Å crystal structure of the largest member, named A6, which is a soluble protein with two distinct domains. The structure of A6 displays a novel protein fold composed mainly of alpha helices. The larger C-terminal domain forms a unique cage that encloses multiple glycerophospholipids with a lipid bilayer-like configuration. The smaller N-terminal domain does not bind lipid but negatively affects lipid binding by A6. Mutations of key hydrophobic residues lining the lipid-binding cage disrupt lipid binding and abolish viral replication. Our results reveal a protein modality for enclosing the lipid bilayer and provide molecular insight into a viral machinery involved in generating and/or stabilizing open-ended membranes.

Original languageEnglish (US)
Pages (from-to)7028-7032
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number27
DOIs
StatePublished - Jul 3 2018

Keywords

  • Crescent membrane
  • Crystal structure
  • Nonvesicular transfer
  • VMAP
  • Vaccinia A6

ASJC Scopus subject areas

  • General

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