5mu2: Difference between revisions
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==ACC1 Fab fragment in complex with CII583-591 (CG10)== | |||
<StructureSection load='5mu2' size='340' side='right' caption='[[5mu2]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5mu2]] is a 24 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MU2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MU2 FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5mu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mu2 OCA], [http://pdbe.org/5mu2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mu2 RCSB], [http://www.ebi.ac.uk/pdbsum/5mu2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mu2 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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<ref>PMID:28679953</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5mu2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Mus musculus]] | |||
[[Category: Dobritzsch, D]] | [[Category: Dobritzsch, D]] | ||
[[Category: Ge, C]] | |||
[[Category: Holmdahl, R]] | [[Category: Holmdahl, R]] | ||
[[Category: | [[Category: Immune system]] | ||
Revision as of 13:34, 13 September 2017
ACC1 Fab fragment in complex with CII583-591 (CG10)ACC1 Fab fragment in complex with CII583-591 (CG10)
Structural highlights
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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