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

Journal of virology | Oct 24, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19656869

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.

Pubmed ID: 19656869 RIS Download

Mesh terms: Animals | Capsid | Cell Line | Dimerization | HIV-1 | Humans | Macaca mulatta | Magnetic Resonance Spectroscopy | Models, Molecular | Mutation | Protein Structure, Tertiary | Proteins | Retroviridae

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Associated grants

  • Agency: NIMH NIH HHS, Id: 1K99MH086162-01
  • Agency: NIAID NIH HHS, Id: AI063987
  • Agency: NIAID NIH HHS, Id: AI076094
  • Agency: NIAID NIH HHS, Id: AI60354
  • Agency: NIMH NIH HHS, Id: K99 MH086162
  • Agency: NIMH NIH HHS, Id: R00 MH086162

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