title: The TRIM5alpha B-box 2 domain promotes cooperative binding to the retroviral capsid by mediating higher-order self-association.
abstract: 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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: 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
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases
references.citation: Nat Cell Biol. 2008 Apr;10(4):422-8
references.pmid: 18327251
references.citation: J Virol. 2002 Jun;76(11):5667-77
references.pmid: 11991995
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10774-9
references.pmid: 15249685
references.citation: J Virol. 2006 Oct;80(19):9754-60
references.pmid: 16973579
references.citation: J Virol. 2005 Dec;79(24):15567-72
references.pmid: 16306627
references.citation: J Cell Biol. 2008 Feb 11;180(3):549-61
references.pmid: 18250195
references.citation: Virology. 2007 Sep 30;366(2):234-44
references.pmid: 17543365
references.citation: Virology. 2006 Sep 15;353(1):234-46
references.pmid: 16808955
references.citation: Cell. 1993 Jun 18;73(6):1067-78
references.pmid: 8513493
references.citation: Mol Cell. 2007 Oct 26;28(2):214-27
references.pmid: 17964261
references.citation: J Mol Biol. 2000 Feb 4;295(5):1139-62
references.pmid: 10653693
references.citation: Virology. 2006 Aug 1;351(2):404-19
references.pmid: 16650449
references.citation: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7465-70
references.pmid: 16648264
references.citation: J Mol Biol. 2007 May 25;369(1):1-10
references.pmid: 17428496
references.citation: Methods Cell Biol. 1994;43 Pt A:99-112
references.pmid: 7823872
references.citation: Virology. 2007 Apr 10;360(2):419-33
references.pmid: 17156811
references.citation: J Virol. 2005 Nov;79(22):14446-50
references.pmid: 16254380
references.citation: Bioessays. 2005 Nov;27(11):1147-57
references.pmid: 16237670
references.citation: J Virol. 2005 Aug;79(16):10571-7
references.pmid: 16051849
references.citation: Virology. 2007 Oct 10;367(1):19-29
references.pmid: 17574642
references.citation: Virology. 2007 Dec 20;369(2):400-10
references.pmid: 17920096
references.citation: J Cell Sci. 1997 Jul;110 ( Pt 14):1563-71
references.pmid: 9247190
references.citation: Gene Ther. 1998 Nov;5(11):1481-7
references.pmid: 9930301
references.citation: Virology. 2006 Jun 5;349(2):300-15
references.pmid: 16472833
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5514-9
references.pmid: 16540544
references.citation: J Virol. 2006 Jul;80(13):6198-206
references.pmid: 16775307
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10780-5
references.pmid: 15249687
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2832-7
references.pmid: 15689398
references.citation: FEBS J. 2008 Apr;275(7):1540-1555
references.pmid: 18312418
references.citation: Virology. 2007 Sep 1;365(2):302-14
references.pmid: 17493656
references.citation: J Virol. 2007 Oct;81(19):10362-78
references.pmid: 17626085
references.citation: J Virol. 2005 Dec;79(24):15175-88
references.pmid: 16306589
references.citation: Science. 1999 Jan 1;283(5398):80-3
references.pmid: 9872746
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10786-91
references.pmid: 15249690
references.citation: J Virol. 2007 Mar;81(5):2138-48
references.pmid: 17135314
references.citation: Biochemistry. 2008 Feb 26;47(8):2450-7
references.pmid: 18220417
references.citation: J Virol. 2006 Jul;80(14):6738-44
references.pmid: 16809279
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11827-32
references.pmid: 15280539
references.citation: J Mol Biol. 1997 Jun 27;269(5):780-95
references.pmid: 9223641
references.citation: J Virol. 2005 Mar;79(5):3139-45
references.pmid: 15709033
references.citation: Curr Biol. 2005 Jan 11;15(1):73-8
references.pmid: 15649369
references.citation: J Biol Chem. 2005 Jul 22;280(29):26933-40
references.pmid: 15897199
references.citation: J Virol. 2005 Jul;79(14):8969-78
references.pmid: 15994791
references.citation: Nature. 2004 Feb 26;427(6977):848-53
references.pmid: 14985764
references.citation: J Mol Biol. 2006 Apr 28;358(2):532-45
references.pmid: 16529770
references.citation: EMBO J. 1995 Apr 3;14(7):1532-41
references.pmid: 7729428
references.citation: Virology. 2005 Dec 20;343(2):201-11
references.pmid: 16183097
references.citation: EMBO J. 2001 May 1;20(9):2140-51
references.pmid: 11331580
references.citation: Mol Cell Biol. 2007 Apr;27(7):2615-24
references.pmid: 17261593