Document Detail


Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1.
MedLine Citation:
PMID:  22902366     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hematopoietic human colony-stimulating factor 1 (hCSF-1) is essential for innate and adaptive immunity against viral and microbial infections and cancer. The human pathogen Epstein-Barr virus secretes the lytic-cycle protein BARF1 that neutralizes hCSF-1 to achieve immunomodulation. Here we show that BARF1 binds the dimer interface of hCSF-1 with picomolar affinity, away from the cognate receptor-binding site, to establish a long-lived complex featuring three hCSF-1 at the periphery of the BARF1 toroid. BARF1 locks dimeric hCSF-1 into an inactive conformation, rendering it unable to signal via its cognate receptor on human monocytes. This reveals a new functional role for hCSF-1 cooperativity in signaling. We propose a new viral strategy paradigm featuring an allosteric decoy receptor of the competitive type, which couples efficient sequestration and inactivation of the host growth factor to abrogate cooperative assembly of the cognate signaling complex.
Authors:
Jonathan Elegheert; Nathalie Bracke; Philippe Pouliot; Irina Gutsche; Alexander V Shkumatov; Nicolas Tarbouriech; Kenneth Verstraete; Anaïs Bekaert; Wim P Burmeister; Dmitri I Svergun; Bart N Lambrecht; Bjorn Vergauwen; Savvas N Savvides
Related Documents :
17101286 - Cnidarian chemical neurotransmission, an updated overview.
16673176 - Regional distribution and relative abundance of serotonin(2c) receptors in human brain:...
6326946 - Serotonin-receptor coupled with membrane electrogenesis in a rat glioma clone.
8022406 - Isolation and characterization of the rat 5-hydroxytryptamine type 2 receptor promoter:...
16722246 - Lessons from the knocked-out glycine transporters.
11606476 - Early impairment of calcium handling and altered expression of junctin in hearts of mic...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-19
Journal Detail:
Title:  Nature structural & molecular biology     Volume:  -     ISSN:  1545-9985     ISO Abbreviation:  Nat. Struct. Mol. Biol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101186374     Medline TA:  Nat Struct Mol Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Unit for Structural Biology, Laboratory for Protein Biochemistry and Biomolecular Engineering, Department of Biochemistry & Microbiology, Ghent University, Ghent, Belgium.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  High levels of peripheral blood circulating plasma cells as a specific risk factor for progression o...
Next Document:  Nectin ectodomain structures reveal a canonical adhesive interface.