5mv3
ACC1 Fab fragment in complex with CII583-591 (CG10)
Structural highlights
DiseaseCO2A1_MOUSE Defects in Col2a1 are the cause of a phenotype resembling human spondyloepiphyseal dysplasia congenita (sedc). Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora and tibias, and retinoschisis and hearing loss. FunctionCO2A1_MOUSE Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces. Publication Abstract from PubMedToday, 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. Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage.,Ge C, Tong D, Liang B, Lonnblom E, Schneider N, Hagert C, Viljanen J, Ayoglu B, Stawikowska R, Nilsson P, Fields GB, Skogh T, Kastbom A, Kihlberg J, Burkhardt H, Dobritzsch D, Holmdahl R JCI Insight. 2017 Jul 6;2(13). pii: 93688. doi: 10.1172/jci.insight.93688. PMID:28679953[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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