5MU2

ACC1 Fab fragment in complex with CII583-591 (CG10)

Summary for 5MU2

• Entry DOI: 10.2210/pdb5mu2/pdb
• Descriptor: ACC1 Fab fragment heavy chain, ACC1 Fab fragment light chain, synthetic peptide containing the CII583-591 epitope of collagen type II, ... (4 entities in total)
• Functional Keywords: anti-citrullinated protein antibody (acpa) fab fragment collagen type ii, immune system
• Biological source: Mus musculus (House mouse); More
• Total number of polymer chains: 24
• Total formula weight: 398186.26

Authors

Dobritzsch, D.,Holmdahl, R.,Ge, C. (deposition date: 2017-01-12, 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

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: 28679953
DOI: 10.1172/jci.insight.93688

Experimental method

X-RAY DIFFRACTION (2.7 Å)