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Journal of Virology, December 2008, p. 11495-11502, Vol. 82, No. 23
0022-538X/08/$08.00+0 doi:10.1128/JVI.01548-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,1 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 021152
Received 22 July 2008/ Accepted 11 September 2008
The retroviral restriction factor, TRIM5
, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5
consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The B-box 2 domain is essential for retrovirus restriction by TRIM5
, but its specific function is unknown. We show here that the B-box 2 domain mediates higher-order self-association of TRIM5
rh oligomers. This self-association increases the efficiency of TRIM5
binding to the retroviral capsid, thus potentiating restriction of retroviral infection. The contribution of the B-box 2 domain to cooperative TRIM5
association with the retroviral capsid explains the conditional nature of the restriction phenotype exhibited by some B-box 2 TRIM5
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 TRIM5
proteins can be achieved.
Published ahead of print on 17 September 2008.
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