Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 15, Pages 6200-6205Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0609174104
Keywords
autoimmunity; familial Mediterranean fever; HIV; TRIM2; TRIM5 alpha
Categories
Funding
- MRC [G9800943, G0401569, MC_U105181010] Funding Source: UKRI
- Medical Research Council [MC_U105181010, G9800943, G0401569] Funding Source: researchfish
- Medical Research Council [G0401569, G9800943, MC_U105181010] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
Ask authors/readers for more resources
The human tripartite motif (TRIM) family comprises 70 members, including HIV restriction factor TRIM5 alpha and disease-associated proteins TRIM20 (pyrin) and TRIM21. TRIM proteins have conserved domain architecture but diverse cellular roles. Here, we describe how the C-terminal PRYSPRY domain mediates diverse TRIM functions. The crystal structure of TRIM21 PRYSPRY in complex with its target IgG Fc reveals a canonical binding interface comprised of two discrete pockets formed by antibody-like variable loops. Alanine scanning of this interface has identified the hot-spot residues that control TRIM21 binding to Fc; the same hot-spots control HIV/murine leukemia virus restriction by TRIM5a and mediate severe familial Mediterranean fever in TRIM20/pyrin. Characterization of the IgG binding site for TRIM21 PRYSPRY reveals TRIM21 as a superantigen analogous to bacterial protein A and suggests that an antibody bipolar bridging mechanism may contribute to the pathogenic accumulation of anti-TRIM21 autoantibody immune complex in autoimmune disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available