The TRIM5alpha B-box 2 domain promotes cooperative binding to the retroviral capsid by mediating higher-order self-association.
The retroviral restriction factor, TRIM5alpha, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5alpha consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The B-box 2 domain is essential for retrovirus restriction by TRIM5alpha, but its specific function is unknown. We show here that the B-box 2 domain mediates higher-order self-association of TRIM5alpha(rh) oligomers. This self-association increases the efficiency of TRIM5alpha binding to the retroviral capsid, thus potentiating restriction of retroviral infection. The contribution of the B-box 2 domain to cooperative TRIM5alpha association with the retroviral capsid explains the conditional nature of the restriction phenotype exhibited by some B-box 2 TRIM5alpha 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 TRIM5alpha proteins can be achieved.
Li
Xing
X
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sodroski
Joseph
J
D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D004285:Dogs; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D017434:Protein Structure, Tertiary; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases
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