A B-box 2 surface patch important for TRIM5α self-association, capsid binding avidity, and retrovirus restriction

Felipe Diaz-Griffero, Xu Rong Qin, Fumiaki Hayashi, Takanori Kigawa, Andres Finzi, Zoe Sarnak, Maritza Lienlaf, Shigeyuki Yokoyama, Joseph Sodroski

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

TRIM5α is a tripartite motif (TRIM) protein that consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The TRIM5αrh 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 TRIM5αrh B-box 2 domain have been associated with alterations in TRIM5αrh 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 TRIM5α 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 TRIM5αrh half-life or the formation of cytoplasmic bodies. Thus, promoting cooperative TRIM5αrh interactions with the HIV-1 capsid represents a major mechanism whereby the B-box 2 domain potentiates HIV-1 restriction.

Original languageEnglish (US)
Pages (from-to)10737-10751
Number of pages15
JournalJournal of virology
Volume83
Issue number20
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Diaz-Griffero, F., Qin, X. R., Hayashi, F., Kigawa, T., Finzi, A., Sarnak, Z., Lienlaf, M., Yokoyama, S., & Sodroski, J. (2009). A B-box 2 surface patch important for TRIM5α self-association, capsid binding avidity, and retrovirus restriction. Journal of virology, 83(20), 10737-10751. https://doi.org/10.1128/JVI.01307-09