1ADQ

CRYSTAL STRUCTURE OF A HUMAN IGM RHEUMATOID FACTOR FAB IN COMPLEX WITH ITS AUTOANTIGEN IGG FC

Summary for 1ADQ

• Entry DOI: 10.2210/pdb1adq/pdb
• Descriptor: IGG4 REA FC, IGM-LAMBDA RF-AN FAB (LIGHT CHAIN), IGM-LAMBDA RF-AN FAB (HEAVY CHAIN) (3 entities in total)
• Functional Keywords: complex (immunoglobulin-autoantigen), rheumatoid factor auto-antibody complex, complex (immunoglobulin-autoantigen) complex, complex (immunoglobulin/autoantigen)
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 70718.08

Authors

Corper, A.L.,Taussig, M.J.,Sutton, B.J. (deposition date: 1997-02-18, release date: 1998-09-16, Last modification date: 2024-10-23)

Primary citation

Corper, A.L.,Sohi, M.K.,Bonagura, V.R.,Steinitz, M.,Jefferis, R.,Feinstein, A.,Beale, D.,Taussig, M.J.,Sutton, B.J.
Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction.
Nat.Struct.Biol., 4:374-381, 1997

PubMed Abstract: Rheumatoid factors are the characteristic autoantibodies of rheumatoid arthritis, which bind to the Fc regions of IgG molecules. Here we report the crystal structure of the Fab fragment of a patient-derived IgM rheumatoid factor (RF-AN) complexed with human IgG4 Fc, at 3.2 A resolution. This is the first structure of an autoantibody-autoantigen complex. The epitope recognised in IgG Fc includes the C gamma 2/C gamma 3 cleft region, and overlaps the binding sites of bacterial Fc-binding proteins. The antibody residues involved in autorecognition are all located at the edge of the conventional combining site surface, leaving much of the latter available, potentially, for recognition of a different antigen. Since an important contact residue is somatic mutation, the structure implicates antigen-driven selection, following somatic mutation of germline genes, in the production of pathogenic rheumatoid factors.

PubMed: 9145108
DOI: 10.1038/nsb0597-374

Experimental method

X-RAY DIFFRACTION (3.15 Å)