7wsl: Difference between revisions
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==PD-1 in complex with Dostarlimab== | ==PD-1 in complex with Dostarlimab== | ||
<StructureSection load='7wsl' size='340' side='right'caption='[[7wsl]]' scene=''> | <StructureSection load='7wsl' size='340' side='right'caption='[[7wsl]], [[Resolution|resolution]] 1.53Å' 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=7WSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WSL FirstGlance]. <br> | <table><tr><td colspan='2'>[[7wsl]] 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=7WSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WSL 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=7wsl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wsl OCA], [https://pdbe.org/7wsl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wsl RCSB], [https://www.ebi.ac.uk/pdbsum/7wsl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wsl ProSAT]</span></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]] 1.534Å</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=7wsl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wsl OCA], [https://pdbe.org/7wsl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wsl RCSB], [https://www.ebi.ac.uk/pdbsum/7wsl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wsl ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== 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 == | |||
[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 == | |||
Targeting of programmed cell death 1 (PD-1) with monoclonal antibodies to block the interaction with its ligand PD-L1 has been successful in immunotherapy of multiple types of cancer, and their mechanism involves the restoration of the T-cell immune response. April 2021, the US FDA approved dostarlimab, a therapeutic antibody against PD-1, for the treatment of endometrial cancer. Here, we report the crystal structure of the extracellular domain of PD-1 in complex with the dostarlimab Fab at the resolution of 1.53 A. Although the interaction between PD-1 and dostarlimab involves mainly the residues within the heavy chain of dostarlimab, the steric occlusion of PD-L1 binding is primarily contributed by the light chain. Dostarlimab induces conformational rearrangements of the BC, C'D and FG loops of PD-1 to achieve a high affinity. Significantly, the residue R86 within the C'D loop of PD-1 plays a critical role for dostarlimab binding by occupying the concave surface on the heavy chain via multiple interactions. This high-resolution structure can provide helpful information for designing improved anti-PD-1 biologics or effective combination strategies for cancer immunotherapy. | |||
Molecular basis of PD-1 blockade by dostarlimab, the FDA-approved antibody for cancer immunotherapy.,Park UB, Jeong TJ, Gu N, Lee HT, Heo YS Biochem Biophys Res Commun. 2022 Apr 9;599:31-37. doi: , 10.1016/j.bbrc.2022.02.026. Epub 2022 Feb 9. PMID:35168061<ref>PMID:35168061</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7wsl" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Cell death protein 3D structures|Cell death protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Heo YS]] | [[Category: Heo YS]] | ||