TRIMCyp cyclophilin domain from Macaca mulatta: HIV-2 CA cyclophilin-binding loop complex
[GAG_HV2RO] Matrix protein p17 targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal. Also mediates nuclear localization of the preintegration complex (By similarity). Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers (By similarity). p6-gag plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1.
Publication Abstract from PubMed
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.
Diverse HIV viruses are targeted by a conformationally dynamic antiviral.,Caines ME, Bichel K, Price AJ, McEwan WA, Towers GJ, Willett BJ, Freund SM, James LC Nat Struct Mol Biol. 2012 Mar 11. doi: 10.1038/nsmb.2253. PMID:22407016
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.