Diverse HIV viruses are targeted by a conformationally dynamic antiviral

Caines, M.E.C., Bichel, K., Price, A.J., McEwan, W.A., Towers, G.J., Willett, B.J. , Freund, S.M.V. and James, L.C. (2012) Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Nature Structural and Molecular Biology, 19(4), pp. 411-416. (doi: 10.1038/nsmb.2253)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Willett, Professor Brian
Authors: Caines, M.E.C., Bichel, K., Price, A.J., McEwan, W.A., Towers, G.J., Willett, B.J., Freund, S.M.V., and James, L.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Structural and Molecular Biology
Publisher:Nature Publishing Group
ISSN:1545-9993
ISSN (Online):1545-9985
Published Online:11 March 2012

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