5t6p: Difference between revisions
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==Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide== | ==Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide== | ||
<StructureSection load='5t6p' size='340' side='right' caption='[[5t6p]], [[Resolution|resolution]] 1.97Å' scene=''> | <StructureSection load='5t6p' size='340' side='right'caption='[[5t6p]], [[Resolution|resolution]] 1.97Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5t6p]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T6P OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5t6p]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T6P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5T6P FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5t6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t6p OCA], [http://pdbe.org/5t6p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t6p RCSB], [http://www.ebi.ac.uk/pdbsum/5t6p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t6p ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Brooks, C L]] | [[Category: Brooks, C L]] | ||
[[Category: Movahedin, M]] | [[Category: Movahedin, M]] | ||
Revision as of 14:23, 16 September 2020
Crystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptideCrystal structure of therapeutic mAB AR20.5 in complex with MUC1 peptide
Structural highlights
Publication Abstract from PubMedIn cancer cells, the glycoprotein Mucin 1 (MUC1) undergoes abnormal, truncated glycosylation. The truncated glycosylation exposes cryptic peptide epitopes that can be recognized by antibodies. Since these immunogenic regions are cancer specific, they represent ideal targets for therapeutic antibodies. We investigated the role of tumor-specific glycosylation on antigen recognition by the therapeutic antibody AR20.5. We explored the affinity of AR20.5 to a synthetic cancer-specific MUC1 glycopeptide and peptide. The antibody bound to the glycopeptide with an order of magnitude stronger affinity than the naked peptide. Given these results, we postulated that AR20.5 must specifically bind the carbohydrate as well as the peptide. Using X-ray crystallography, we examined this hypothesis by determining the structure of AR20.5 in complex with both peptide and glycopeptide. Surprisingly, the structure revealed that the carbohydrate did not form any specific polar contacts with the antibody. The high affinity of AR20.5 for the glycopeptide and the lack of specific binding contacts support a hypothesis that glycosylation of MUC1 stabilizes an extended bioactive conformation of the peptide recognized by the antibody. Since high affinity binding of AR20.5 to the MUC1 glycopeptide may not driven by specific antibody-antigen contacts, but rather evidence suggests that glycosylation alters the conformational equilibrium of the antigen, which allows the antibody to select the correct conformation. This study suggests a novel mechanism of antibody-antigen interaction and also suggests that glycosylation of MUC1 is important for the generation of high affinity therapeutic antibodies. Glycosylation of MUC1 influences the binding of a therapeutic antibody by altering the conformational equilibrium of the antigen.,Movahedin M, Brooks TM, Supekar NT, Gokanapudi N, Boons GJ, Brooks CL Glycobiology. 2016 Dec 26. pii: cww131. doi: 10.1093/glycob/cww131. PMID:28025250[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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