2W65

Anti citrullinated Collagen type 2 antibody acc4 in complex with a citrullinated peptide

Summary for 2W65

• Entry DOI: 10.2210/pdb2w65/pdb
• Related: 2W60
• Descriptor: ANTI-CITRULLINATED COLLAGEN TYPE II FAB ACC4, COLLAGEN DERIVED PEPTIDE PCII-CIT1, SULFATE ION, ... (5 entities in total)
• Functional Keywords: arthritis, collagen type ii, antibody anti-citrullin, immune system
• Biological source: MUS MUSCULUS (MOUSE); More
• Total number of polymer chains: 6
• Total formula weight: 96806.26

Authors

Uysal, H.,Bockermann, R.,Nandakumar, K.S.,Sehnert, B.,Bajtner, E.,Engstrom, A.,Serre, G.,Burkhardt, H.,Thunnissen, M.M.G.M.,Holmdahl, R. (deposition date: 2008-12-17, release date: 2009-02-24, Last modification date: 2023-12-13)

Primary citation

Uysal, H.,Bockermann, R.,Nandakumar, K.S.,Sehnert, B.,Bajtner, E.,Engstrom, A.,Serre, G.,Burkhardt, H.,Thunnissen, M.M.,Holmdahl, R.
Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis.
J. Exp. Med., 206:449-462, 2009

PubMed Abstract: 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.

PubMed: 19204106
DOI: 10.1084/jem.20081862

Experimental method

X-RAY DIFFRACTION (2.21 Å)