5MU0

ACC1 Fab fragment in complex with citrullinated C1 epitope of CII (IA03)

5MU0 の概要

• エントリーDOI: 10.2210/pdb5mu0/pdb
• 分子名称: heavy chain of ACC1 antibody Fab fragment, light chain of ACC1 antibody Fab fragment, IA03 peptide containing the citrullinated C1 epitope of collagen type II,Collagen alpha-1(II) chain,IA03 peptide containing the citrullinated C1 epitope of collagen type II, ... (4 entities in total)
• 機能のキーワード: anti-citrullinated protein antibody (acpa) fab fragment collagen type ii citrullinated c1 epitope, immune system
• 由来する生物種: Mus musculus (House mouse); 詳細
• タンパク質・核酸の鎖数: 24
• 化学式量合計: 390033.06

構造登録者

Dobritzsch, D.,Holmdahl, R.,Ge, C. (登録日: 2017-01-11, 公開日: 2017-07-19, 最終更新日: 2024-01-17)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)