Document Detail

ESCRT-III CHMP2A and CHMP3 form variable helical polymers in vitro and act synergistically during HIV-1 budding.
MedLine Citation:
PMID:  23051622     Owner:  NLM     Status:  MEDLINE    
The endosomal sorting complex required for transport-III (ESCRT-III) proteins are essential for budding of some enveloped viruses, for the formation of intraluminal vesicles at the endosome and for the abscission step of cytokinesis. ESCRT-III proteins form polymers that constrict membrane tubes, leading to fission. We have used electron cryomicroscopy to determine the molecular organization of pleiomorphic ESCRT-III CHMP2A-CHMP3 polymers. The three-dimensional reconstruction at 22 Å resolution reveals a helical organization of filaments of CHMP molecules organized in a head-to-tail fashion. Protease susceptibility experiments indicate that polymerization is achieved via conformational changes that increase the protomer stability. Combinatorial siRNA knockdown experiments indicate that CHMP3 contributes synergistically to HIV-1 budding, and the CHMP3 contribution is ~ 10-fold more pronounced in concert with CHMP2A than with CHMP2B. This is consistent with surface plasmon resonance affinity measurements that suggest sequential CHMP4B-CHMP3-CHMP2A recruitment while showing that both CHMP2A and CHMP2B interact with CHMP4B, in agreement with their redundant functions in HIV-1 budding. Our data thus indicate that the CHMP2A-CHMP3 polymer observed in vitro contributes to HIV-1 budding by assembling on CHMP4B polymers.
Grégory Effantin; Aurélien Dordor; Virginie Sandrin; Nicolas Martinelli; Wesley I Sundquist; Guy Schoehn; Winfried Weissenhorn
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-06
Journal Detail:
Title:  Cellular microbiology     Volume:  15     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  2013-06-17     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  213-26     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
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MeSH Terms
Cryoelectron Microscopy
Endosomal Sorting Complexes Required for Transport / chemistry*,  metabolism,  ultrastructure
HIV-1 / chemistry*,  physiology
Models, Molecular
Peptide Hydrolases / chemistry
Promoter Regions, Genetic
Protein Binding
Protein Multimerization
Protein Structure, Secondary
RNA, Small Interfering / genetics
Recombinant Proteins / chemistry,  metabolism,  ultrastructure
Surface Plasmon Resonance
Virus Release / physiology*
Grant Support
P50 6M 082545//PHS HHS; P50 GM082545/GM/NIGMS NIH HHS; R01 AI051174/AI/NIAID NIH HHS; R0I AI051174/AI/NIAID NIH HHS
Reg. No./Substance:
0/CHMP2A protein, human; 0/CHMP2B protein, human; 0/CHMP3 protein, human; 0/CHMP4B protein, human; 0/Endosomal Sorting Complexes Required for Transport; 0/RNA, Small Interfering; 0/Recombinant Proteins; EC 3.4.-/Peptide Hydrolases

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