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Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2494-9. doi: 10.1073/pnas.1318962111. Epub 2014 Feb 3.

The tripartite motif coiled-coil is an elongated antiparallel hairpin dimer.

Author information

1
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.

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.

KEYWORDS:

X-ray crystallography; antiparallel dimer; disulfide crosslinking

PMID:
24550273
PMCID:
PMC3932864
DOI:
10.1073/pnas.1318962111
[Indexed for MEDLINE]
Free PMC Article

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