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

103 Citations (Scopus)

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 2009
Externally publishedYes

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Retroviridae
capsid
Capsid
Human immunodeficiency virus 1
HIV-1
Virus Diseases
reverse transcription
Macaca mulatta
infection
cooperatives
Reverse Transcription
half life
arginine
Half-Life
Arginine
nuclear magnetic resonance spectroscopy
inactivation
Magnetic Resonance Spectroscopy
proteins
viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

A B-box 2 surface patch important for TRIM5α self-association, capsid binding avidity, and retrovirus restriction. / Diaz-Griffero, Felipe; Qin, Xu Rong; Hayashi, Fumiaki; Kigawa, Takanori; Finzi, Andres; Sarnak, Zoe; Lienlaf, Maritza; Yokoyama, Shigeyuki; Sodroski, Joseph.

In: Journal of Virology, Vol. 83, No. 20, 10.2009, p. 10737-10751.

Research output: Contribution to journalArticle

Diaz-Griffero, F, Qin, XR, 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, vol. 83, no. 20, pp. 10737-10751. https://doi.org/10.1128/JVI.01307-09
Diaz-Griffero, Felipe ; Qin, Xu Rong ; Hayashi, Fumiaki ; Kigawa, Takanori ; Finzi, Andres ; Sarnak, Zoe ; Lienlaf, Maritza ; Yokoyama, Shigeyuki ; Sodroski, Joseph. / A B-box 2 surface patch important for TRIM5α self-association, capsid binding avidity, and retrovirus restriction. In: Journal of Virology. 2009 ; Vol. 83, No. 20. pp. 10737-10751.
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