TRIM21 is a trimeric protein that binds IgG Fc via the B30.2 domain.
TRIMs comprise a large protein family that include anti-retroviral restriction factors such as TRIM5alpha. Auto-antibodies to TRIM21 (Ro52) are a common serological feature of patients with Sjogren's syndrome and systemic lupus erythematosus (SLE). We show that, in addition to this autoantibody response, TRIM21 binds specifically to the Fc region of human IgG isotypes 1, 2 and 4, via a conformation dependent interaction. The minimal binding epitope was identified as the C-terminal B30.2 domain. The interaction was independent of N-linked glycosylation of the IgG CH2 domain. TRIM21 formed a trimer that competed with protein A for binding to IgG Fc. We conclude that TRIM21 binds to the consensus CH2/CH3 domain interface in the Fc region, overlapping the binding site of several other proteins, including Staphylococcus aureus protein A and Streptococcus spp. protein G. The data suggest that the normal function of TRIM21 involves regulation of IgG functions and that TRIM/B30.2 molecules may have broader and unsuspected roles in innate immunity, beyond that of retroviral restriction.
Rhodes
David A
DA
Department of Pathology, Immunology Division, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK. dar32@cam.ac.uk
Trowsdale
John
J
D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D002241:Carbohydrates; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007129:Immunoglobulin Gm Allotypes / Q000276:immunology; D019169:Jurkat Cells; D051379:Mice; D009687:Nuclear Proteins; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012261:Ribonucleoproteins; D013205:Staphylococcal Protein A / Q000378:metabolism; D000099207:SS-A Antigen
D002241:Carbohydrates; D004268:DNA-Binding Proteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007129:Immunoglobulin Gm Allotypes; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D013205:Staphylococcal Protein A; D000099207:SS-A Antigen