5ocx
From Proteopedia
(Difference between revisions)
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==Crystal structure of ACPA E4 in complex with CII-C-13-CIT== | ==Crystal structure of ACPA E4 in complex with CII-C-13-CIT== | ||
| - | <StructureSection load='5ocx' size='340' side='right' caption='[[5ocx]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='5ocx' size='340' side='right'caption='[[5ocx]], [[Resolution|resolution]] 1.75Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5ocx]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ocx]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCX FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIR:CITRULLINE'>CIR</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=5ocx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocx OCA], [http://pdbe.org/5ocx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ocx RCSB], [http://www.ebi.ac.uk/pdbsum/5ocx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocx ProSAT]</span></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=5ocx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ocx OCA], [http://pdbe.org/5ocx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ocx RCSB], [http://www.ebi.ac.uk/pdbsum/5ocx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ocx ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. METHODS: Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. RESULTS: Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. CONCLUSION: These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs. | ||
| + | |||
| + | Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies.,Ge C, Xu B, Liang B, Lonnblom E, Lundstrom SL, Zubarev RA, Ayoglu B, Nilsson P, Skogh T, Kastbom A, Malmstrom V, Klareskog L, Toes REM, Rispens T, Dobritzsch D, Holmdahl R Arthritis Rheumatol. 2019 Feb;71(2):210-221. doi: 10.1002/art.40698. Epub 2019, Jan 4. PMID:30152126<ref>PMID:30152126</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5ocx" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Dobritzsch, D]] | [[Category: Dobritzsch, D]] | ||
[[Category: Ge, C]] | [[Category: Ge, C]] | ||
Revision as of 06:08, 7 August 2019
Crystal structure of ACPA E4 in complex with CII-C-13-CIT
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