5MV4
ACC1 Fab fragment in complex with citrullinated CII616-639 epitope of collagen type II (ptm23)
Summary for 5MV4
| Entry DOI | 10.2210/pdb5mv4/pdb |
| Descriptor | ACC1 antibody Fab fragment, heavy chain, ACC1 antibody Fab fragment, light chain, synthetic peptide containing the citrullinated collagen type II epitope CII616-639,Collagen alpha-1(II) chain,synthetic peptide containing the citrullinated collagen type II epitope CII616-639, ... (5 entities in total) |
| Functional Keywords | anti-citrullinated protein antibody (acpa) fab fragment collagen type ii citrullinated c1 epitope, immune system |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 24 |
| Total formula weight | 410469.96 |
| Authors | Dobritzsch, D.,Holmdahl, R.,Ge, C. (deposition date: 2017-01-15, release date: 2017-07-19, Last modification date: 2024-01-17) |
| Primary citation | Ge, C.,Tong, D.,Liang, B.,Lonnblom, E.,Schneider, N.,Hagert, C.,Viljanen, J.,Ayoglu, B.,Stawikowska, R.,Nilsson, P.,Fields, G.B.,Skogh, T.,Kastbom, A.,Kihlberg, J.,Burkhardt, H.,Dobritzsch, D.,Holmdahl, R. Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage. JCI Insight, 2:-, 2017 Cited by PubMed Abstract: Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis. PubMed: 28679953DOI: 10.1172/jci.insight.93688 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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