PDBsum entry 2iwg

Immunoglobulin domain

PDB id: 2iwg

Contents

Protein chains

207 a.a.

181 a.a.

Ligands

NAG-NAG-BMA-MAN-NAG-GAL-MAN ×2

FUC ×2

Waters ×172

References listed in PDB file

Key reference

Title

Structural basis for pryspry-Mediated tripartite motif (trim) protein function.

Authors

L.C.James, A.H.Keeble, Z.Khan, D.A.Rhodes, J.Trowsdale.

Ref.

Proc Natl Acad Sci U S A, 2007, 104, 6200-6205. [DOI no: 10.1073/pnas.0609174104]

PubMed id

17400754

Note: In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above have been manually determined.

Abstract

The human tripartite motif (TRIM) family comprises 70 members, including HIV restriction factor TRIM5alpha 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 TRIM5alpha 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.

Figure 1.

Figure 4.