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PDBsum entry 2w65
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Immune system
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PDB id
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2w65
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References listed in PDB file
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Key reference
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Title
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Structure and pathogenicity of antibodies specific for citrullinated collagen type ii in experimental arthritis.
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Authors
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H.Uysal,
R.Bockermann,
K.S.Nandakumar,
B.Sehnert,
E.Bajtner,
A.Engström,
G.Serre,
H.Burkhardt,
M.M.Thunnissen,
R.Holmdahl.
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Ref.
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J Exp Med, 2009,
206,
449-462.
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PubMed id
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Abstract
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Antibodies to citrulline-modified proteins have a high diagnostic value in
rheumatoid arthritis (RA). However, their biological role in disease development
is still unclear. To obtain insight into this question, a panel of mouse
monoclonal antibodies was generated against a major triple helical collagen type
II (CII) epitope (position 359-369; ARGLTGRPGDA) with or without arginines
modified by citrullination. These antibodies bind cartilage and synovial tissue,
and mediate arthritis in mice. Detection of citrullinated CII from RA patients'
synovial fluid demonstrates that cartilage-derived CII is indeed citrullinated
in vivo. The structure determination of a Fab fragment of one of these
antibodies in complex with a citrullinated peptide showed a surprising beta-turn
conformation of the peptide and provided information on citrulline recognition.
Based on these findings, we propose that autoimmunity to CII, leading to the
production of antibodies specific for both native and citrullinated CII, is an
important pathogenic factor in the development of RA.
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