title: Functional replacement of the RING, B-box 2, and coiled-coil domains of tripartite motif 5alpha (TRIM5alpha) by heterologous TRIM domains.
abstract: Tripartite motif 5alpha (TRIM5alpha) restricts some retroviruses, including human immunodeficiency virus type 1 (HIV-1), from infecting the cells of particular species. TRIM5alpha is a member of the TRIM family of proteins, which contain RING, B-box, coiled-coil (CC), and, in some cases, B30.2(SPRY) domains. Here we investigated the abilities of domains from TRIM proteins (TRIM6, TRIM34, and TRIM21) that do not restrict HIV-1 infection to substitute for the domains of rhesus monkey TRIM5alpha (TRIM5alpha(rh)). The RING, B-box 2, and CC domains of the paralogous TRIM6 and TRIM34 proteins functionally replaced the corresponding TRIM5alpha(rh) domains, allowing HIV-1 restriction. By contrast, similar chimeras containing the components of TRIM21, a slightly more distant relative of TRIM5, did not restrict HIV-1 infection. The TRIM21 B-box 2 domain and its flanking linker regions contributed to the functional defectiveness of these chimeras. All of the chimeric proteins formed trimers. All of the chimeras that restricted HIV-1 infection bound the assembled HIV-1 capsid complexes. These results indicate that heterologous RING, B-box 2, and CC domains from related TRIM proteins can functionally substitute for TRIM5alpha(rh) domains.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street-JFB 824, Boston, MA 02115, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Matthew
authors.initials: M
authors.lastname: Stremlau
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D050506:Mutant Chimeric Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D019251:Nucleocapsid / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012261:Ribonucleoproteins; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D000099207:SS-A Antigen
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D050506:Mutant Chimeric Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012261:Ribonucleoproteins; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000099207:SS-A Antigen; C417918:TRIM34 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; C000591243:TRIM6 protein, human