Dynamic conformational changes in the rhesus TRIM5alpha dimer dictate the potency of HIV-1 restriction Journal Article

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Authors: Lamichhane, R.; Mukherjee, S; Smolin, N; Pauszek, R. F., 3rd; Bradley, M; Sastri, J.; Robia, S. L.; Millar, D; Campbell, E. M.
Article Title: Dynamic conformational changes in the rhesus TRIM5alpha dimer dictate the potency of HIV-1 restriction
Abstract: The TRIM5alpha protein from rhesus macaques (rhTRIM5alpha) mediates a potent inhibition of HIV-1 infection via a mechanism that involves the abortive disassembly of the viral core. We have demonstrated that alpha-helical elements within the Linker 2 (L2) region, which lies between the SPRY domain and the Coiled-Coil domain, influence the potency of restriction. Here, we utilize single-molecule FRET analysis to reveal that the L2 region of the TRIM5alpha dimer undergoes dynamic conformational changes, which results in the displacement of L2 regions by 25 angstroms relative to each other. Analysis of restriction enhancing or abrogating mutations in the L2 region reveal that restriction defective mutants are unable to undergo dynamic conformational changes and do not assume compact, alpha-helical conformations in the L2 region. These data suggest a model in which conformational changes in the L2 region mediate displacement of CA bound SPRY domains to induce the destabilization of assembled capsid during restriction.
Journal Title: Virology
Volume: 500
ISSN: 1096-0341; 0042-6822
Publisher: Elsevier Inc  
Journal Place: United States
Date Published: 2017
Start Page: 161
End Page: 168
Language: eng
DOI/URL:

S0042-6822(16)30295-1
Notes: LR: 20170303; CI: Copyright A(c) 2016; GR: G20 RR030939/RR/NCRR NIH HHS/United States; GR: P50 GM082545/GM/NIGMS NIH HHS/United States; GR: R01 AI093258/AI/NIAID NIH HHS/United States; GR: R01 HL092321/HL/NHLBI NIH HHS/United States; JID: 0110674; NIHMS828242; OTO: NOTNLM; PMCR: 2018/01/01; 2016/07/25 [received]; 2016/10/01 [revised]; 2016/10/05 [accepted]; ppublish