title: The tripartite motif coiled-coil is an elongated antiparallel hairpin dimer.
abstract: Tripartite motif (TRIM) proteins make up a large family of coiled-coil-containing RING E3 ligases that function in many cellular processes, particularly innate antiviral response pathways. Both dimerization and higher-order assembly are important elements of TRIM protein function, but the atomic details of TRIM tertiary and quaternary structure have not been fully understood. Here, we present crystallographic and biochemical analyses of the TRIM coiled-coil and show that TRIM proteins dimerize by forming interdigitating antiparallel helical hairpins that position the N-terminal catalytic RING domains at opposite ends of the dimer and the C-terminal substrate-binding domains at the center. The dimer core comprises an antiparallel coiled-coil with a distinctive, symmetric pattern of flanking heptad and central hendecad repeats that appear to be conserved across the entire TRIM family. Our studies reveal how the coiled-coil organizes TRIM25 to polyubiquitylate the RIG-I/viral RNA recognition complex and how dimers of the TRIM5α protein are arranged within hexagonal arrays that recognize the HIV-1 capsid lattice and restrict retroviral replication.
authors.affiliation: Department of Molecular Physiology and Biological Physics and The Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908.
authors.forename: Jacint G
authors.initials: JG
authors.lastname: Sanchez
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Okreglicka
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Chandrasekaran
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Welker
authors.forename: Wesley I
authors.initials: WI
authors.lastname: Sundquist
authors.forename: Owen
authors.initials: O
authors.lastname: Pornillos
mesh_terms: D001483:Base Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D019143:Evolution, Molecular; D005470:Fluorometry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D012394:Rosaniline Dyes; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics*; D014461:Ultracentrifugation
chemical_list: D012394:Rosaniline Dyes; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C048139:Coomassie blue; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: X-ray crystallography; antiparallel dimer; disulfide crosslinking