Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5α B-box 2 domain

Felipe Diaz-Griffero, Alak Kar, Michel Perron, Shi-Hua Xiang, Hassan Javanbakht, Xing Li, Joseph Sodroski

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

An intact B-box 2 domain is essential for the antiretroviral activity of TRIM5α. We modeled the structure of the B-box 2 domain of TRIM5α based on the existing three-dimensional structure of the B-box 2 domain of human TRIM29. Using this model, we altered the residues predicted to be exposed on the surface of this globular structure. Most of the alanine substitutions in these residues exerted little effect on the antiretroviral activity of human TRIM5αhu or rhesus monkey TRIM5αrh. However, alteration of arginine 119 of TRIM5αhu or the corresponding arginine 121 of TRIM5αrh diminished the abilities of the proteins to restrict retroviral infection without affecting trimerization or recognition of the viral capsid. The abilities of these functionally defective TRIM5α proteins to accelerate the uncoating of the targeted retroviral capsid were abolished. Removal of the positively charged side chain from B-box 2 arginines 119/120/121 resulted in diminished proteasome-independent turnover of TRIM5α and the related restriction factor TRIMCyp. However, testing of an array of mutants revealed that the rapid turnover and retroviral restriction functions of this B-box 2 region are separable.

Original languageEnglish (US)
Pages (from-to)10362-10378
Number of pages17
JournalJournal of virology
Volume81
Issue number19
DOIs
StatePublished - Oct 1 2007

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Proteasome Inhibitors
proteasome endopeptidase complex
arginine
Arginine
capsid
Capsid
Proteasome Endopeptidase Complex
Macaca mulatta
Human Activities
Alanine
alanine
Proteins
proteins
mutants
Infection
infection
testing
antiretroviral properties

ASJC Scopus subject areas

  • Immunology

Cite this

Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5α B-box 2 domain. / Diaz-Griffero, Felipe; Kar, Alak; Perron, Michel; Xiang, Shi-Hua; Javanbakht, Hassan; Li, Xing; Sodroski, Joseph.

In: Journal of virology, Vol. 81, No. 19, 01.10.2007, p. 10362-10378.

Research output: Contribution to journalArticle

Diaz-Griffero, Felipe ; Kar, Alak ; Perron, Michel ; Xiang, Shi-Hua ; Javanbakht, Hassan ; Li, Xing ; Sodroski, Joseph. / Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5α B-box 2 domain. In: Journal of virology. 2007 ; Vol. 81, No. 19. pp. 10362-10378.
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