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Diverse HIV viruses are targeted by a conformationally dynamic antiviral

DOI: 10.1038/nsmb.2253 DOI Help
PMID: 22407016 PMID Help

Authors: Matthew Caines (MRC Laboratory of Molecular Biology) , Katsiaryna Bichel (MRC) , Amanda J Price (MRC) , William A Mcewan (MRC) , Greg J Towers (MRC) , Brian J Willett (University of Glasgow) , Stefan M V Freund (MRC) , Leo C James (MRC)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 19 (4) , PAGES 411 - 416

State: Published (Approved)
Published: March 2012

Abstract: Rhesus macaque TRIMCyp (RhTC) is a potent primate antiviral host protein that inhibits the replication of diverse HIV viruses. Here we show that it has acquired the ability to target multiple viruses by evolving an active site that interconverts between multiple conformations. Mutations that have relieved active site constraints allow RhTC to dynamically sample conformational space, including radically different conformers that target both HIV-1 and HIV-2 viruses. Introduction of a reversible constraint into RhTC allows specificity to be switched between a single conformation specific for HIV-1 and a dynamic ensemble that targets multiple viruses. These results show that conformational diversity can be used to expand the target diversity of innate immune receptors by supplementing their limited genetic variability with variability in protein structure

Journal Keywords: Cyclophilin; HIV; HIV; Host-Pathogen; Immunity; Innate; Macaca; Models; Molecular; Protein; Protein Conformation

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

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