The TRIM5α B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association
-
- Xing Li
- Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115
-
- Joseph Sodroski
- Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115
説明
<jats:title>ABSTRACT</jats:title> <jats:p> The retroviral restriction factor, TRIM5α, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5α consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The B-box 2 domain is essential for retrovirus restriction by TRIM5α, but its specific function is unknown. We show here that the B-box 2 domain mediates higher-order self-association of TRIM5α <jats:sub>rh</jats:sub> oligomers. This self-association increases the efficiency of TRIM5α binding to the retroviral capsid, thus potentiating restriction of retroviral infection. The contribution of the B-box 2 domain to cooperative TRIM5α association with the retroviral capsid explains the conditional nature of the restriction phenotype exhibited by some B-box 2 TRIM5α mutants; the potentiation of capsid binding that results from B-box 2-mediated self-association is essential for restriction when B30.2(SPRY) domain-mediated interactions with the retroviral capsid are weak. Thus, B-box 2-dependent higher-order self-association and B30.2(SPRY)-dependent capsid binding represent complementary mechanisms whereby sufficiently dense arrays of capsid-bound TRIM5α proteins can be achieved. </jats:p>
収録刊行物
-
- Journal of Virology
-
Journal of Virology 82 (23), 11495-11502, 2008-12
American Society for Microbiology
