5wt9
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==Complex structure of PD-1 and nivolumab-Fab== | ==Complex structure of PD-1 and nivolumab-Fab== | ||
| - | <StructureSection load='5wt9' size='340' side='right' caption='[[5wt9]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5wt9' size='340' side='right'caption='[[5wt9]], [[Resolution|resolution]] 2.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5wt9]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WT9 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5wt9]] is a 3 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=5WT9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WT9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.401Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5wt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wt9 OCA], [https://pdbe.org/5wt9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wt9 RCSB], [https://www.ebi.ac.uk/pdbsum/5wt9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wt9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM:[https://omim.org/entry/605218 605218]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.<ref>PMID:12402038</ref> |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN] Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. Possible cell death inducer, in association with other factors.<ref>PMID:21276005</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cancer immunotherapy by targeting of immune checkpoint molecules has been a research 'hot-spot' in recent years. Nivolumab, a human monoclonal antibody targeting PD-1, has been widely used clinically since 2014. However, the binding mechanism of nivolumab to PD-1 has not yet been shown, despite a recent report describing the complex structure of pembrolizumab/PD-1. It has previously been speculated that PD-1 glycosylation is involved in nivolumab recognition. Here we report the complex structure of nivolumab with PD-1 and evaluate the effects of PD-1 N-glycosylation on the interactions with nivolumab. Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all. Nivolumab binds to a completely different area than pembrolizumab. These results provide the basis for the design of future inhibitory molecules targeting PD-1. | ||
| + | |||
| + | An unexpected N-terminal loop in PD-1 dominates binding by nivolumab.,Tan S, Zhang H, Chai Y, Song H, Tong Z, Wang Q, Qi J, Wong G, Zhu X, Liu WJ, Gao S, Wang Z, Shi Y, Yang F, Gao GF, Yan J Nat Commun. 2017 Feb 6;8:14369. doi: 10.1038/ncomms14369. PMID:28165004<ref>PMID:28165004</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5wt9" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Cell death protein 3D structures|Cell death protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Chai | + | [[Category: Homo sapiens]] |
| - | [[Category: Gao | + | [[Category: Large Structures]] |
| - | [[Category: Gao | + | [[Category: Chai Y]] |
| - | [[Category: Liu | + | [[Category: Gao GF]] |
| - | [[Category: Qi | + | [[Category: Gao S]] |
| - | [[Category: Shi | + | [[Category: Liu WJ]] |
| - | [[Category: Song | + | [[Category: Qi J]] |
| - | [[Category: Tan | + | [[Category: Shi Y]] |
| - | [[Category: Tong | + | [[Category: Song H]] |
| - | [[Category: Wang | + | [[Category: Tan S]] |
| - | [[Category: Wang | + | [[Category: Tong Z]] |
| - | [[Category: Wong | + | [[Category: Wang Q]] |
| - | [[Category: Yan | + | [[Category: Wang Z]] |
| - | [[Category: Yang | + | [[Category: Wong G]] |
| - | [[Category: Zhang | + | [[Category: Yan J]] |
| - | [[Category: Zhu | + | [[Category: Yang F]] |
| - | + | [[Category: Zhang H]] | |
| - | + | [[Category: Zhu X]] | |
| - | + | ||
Current revision
Complex structure of PD-1 and nivolumab-Fab
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