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A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction.

Authors
  • Diaz-Griffero, Felipe
  • Qin, Xu-rong
  • Hayashi, Fumiaki
  • Kigawa, Takanori
  • Finzi, Andres
  • Sarnak, Zoe
  • Lienlaf, Maritza
  • Yokoyama, Shigeyuki
  • Sodroski, Joseph
Type
Published Article
Journal
Journal of Virology
Publisher
American Society for Microbiology
Publication Date
Oct 01, 2009
Volume
83
Issue
20
Pages
10737–10751
Identifiers
DOI: 10.1128/JVI.01307-09
PMID: 19656869
Source
Medline
License
Unknown

Abstract

TRIM5alpha is a tripartite motif (TRIM) protein that consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The TRIM5alpha(rh) protein from rhesus monkeys recognizes the human immunodeficiency virus type 1 (HIV-1) capsid as it enters the host cell and blocks virus infection prior to reverse transcription. HIV-1-restricting ability can be eliminated by disruption of the B-box 2 domain. Changes in the TRIM5alpha(rh) B-box 2 domain have been associated with alterations in TRIM5alpha(rh) turnover, the formation of cytoplasmic bodies and higher-order oligomerization. We present here the nuclear magnetic resonance structure of the TRIM5 B-box 2 domain and identify an unusual hydrophobic patch (cluster 1) on the domain surface. Alteration of cluster 1 or the flanking arginine 121 resulted in various degrees of inactivation of HIV-1 restriction, in some cases depending on compensatory changes in other nearby charged residues. For this panel of TRIM5alpha(rh) B-box 2 mutants, inhibition of HIV-1 infection was strongly correlated with higher-order self-association and binding affinity for capsid complexes but not with TRIM5alpha(rh) half-life or the formation of cytoplasmic bodies. Thus, promoting cooperative TRIM5alpha(rh) interactions with the HIV-1 capsid represents a major mechanism whereby the B-box 2 domain potentiates HIV-1 restriction.

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