6tkf
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==ChiLob 7/4 H2 HC-C225S KappaLC-C214S F(ab')2== |
| - | <StructureSection load='6tkf' size='340' side='right'caption='[[6tkf]]' scene=''> | + | <StructureSection load='6tkf' size='340' side='right'caption='[[6tkf]], [[Resolution|resolution]] 2.18Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6tkf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TKF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TKF FirstGlance]. <br> |
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tkf OCA], [https://pdbe.org/6tkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tkf RCSB], [https://www.ebi.ac.uk/pdbsum/6tkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tkf ProSAT]</span></td></tr> | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tkf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tkf OCA], [https://pdbe.org/6tkf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tkf RCSB], [https://www.ebi.ac.uk/pdbsum/6tkf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tkf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Antibodies protect from infection, underpin successful vaccines and elicit therapeutic responses in otherwise untreatable cancers and autoimmune conditions. The human IgG2 isotype displays a unique capacity to undergo disulfide shuffling in the hinge region, leading to modulation of its ability to drive target receptor signaling (agonism) in a variety of important immune receptors, through hitherto unexplained molecular mechanisms. To address the underlying process and reveal how hinge disulfide orientation affects agonistic activity, we generated a series of cysteine to serine exchange variants in the hinge region of the clinically relevant monoclonal antibody ChiLob7/4, directed against the key immune receptor CD40. We report how agonistic activity varies with disulfide pattern and is afforded by the presence of a disulfide crossover between F(ab) arms in the agonistic forms, independently of epitope, as observed in the determined crystallographic structures. This structural "switch" affects directly on antibody conformation and flexibility. Small-angle x-ray scattering and ensemble modeling demonstrated that the least flexible variants adopt the fewest conformations and evoke the highest levels of receptor agonism. This covalent change may be amenable for broad implementation to modulate receptor signaling in an epitope-independent manner in future therapeutics. | ||
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| + | Hinge disulfides in human IgG2 CD40 antibodies modulate receptor signaling by regulation of conformation and flexibility.,Orr CM, Fisher H, Yu X, Chan CH, Gao Y, Duriez PJ, Booth SG, Elliott I, Inzhelevskaya T, Mockridge I, Penfold CA, Wagner A, Glennie MJ, White AL, Essex JW, Pearson AR, Cragg MS, Tews I Sci Immunol. 2022 Jul 15;7(73):eabm3723. doi: 10.1126/sciimmunol.abm3723. Epub , 2022 Jul 8. PMID:35857577<ref>PMID:35857577</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6tkf" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Fisher H]] |
| + | [[Category: Orr CM]] | ||
| + | [[Category: Tews I]] | ||
Revision as of 10:04, 21 December 2022
ChiLob 7/4 H2 HC-C225S KappaLC-C214S F(ab')2
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