5ius: Difference between revisions
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<StructureSection load='5ius' size='340' side='right'caption='[[5ius]], [[Resolution|resolution]] 2.89Å' scene=''> | <StructureSection load='5ius' size='340' side='right'caption='[[5ius]], [[Resolution|resolution]] 2.89Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ius]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5ius]] is a 4 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=5IUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IUS FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.889Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ius FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ius OCA], [https://pdbe.org/5ius PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ius RCSB], [https://www.ebi.ac.uk/pdbsum/5ius PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ius 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Cell death protein|Cell death protein]] | *[[Cell death protein 3D structures|Cell death protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bowman | [[Category: Bowman GR]] | ||
[[Category: Kao | [[Category: Kao J]] | ||
[[Category: Kruse | [[Category: Kruse AC]] | ||
[[Category: Maute | [[Category: Maute R]] | ||
[[Category: Pascolutti | [[Category: Pascolutti R]] | ||
[[Category: Ring | [[Category: Ring AM]] | ||
[[Category: Sun | [[Category: Sun X]] | ||
Latest revision as of 13:32, 6 September 2023
Crystal structure of human PD-L1 in complex with high affinity PD-1 mutantCrystal structure of human PD-L1 in complex with high affinity PD-1 mutant
Structural highlights
DiseasePDCD1_HUMAN Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM: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.[1] FunctionPDCD1_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.[2] Publication Abstract from PubMedThe immune checkpoint receptor PD-1 and its ligand, PD-L1, have emerged as key regulators of anti-tumor immunity in humans. Recently, we reported an ultra-high-affinity PD-1 mutant, termed high-affinity consensus (HAC) PD-1, which shows superior therapeutic efficacy in mice compared with antibodies. However, the molecular details underlying the action of this agent remain incompletely understood, and a molecular view of PD-1/PD-L1 interactions in general is only beginning to emerge. Here, we report the structure of HAC PD-1 in complex with PD-L1, showing that it binds PD-L1 using a unique set of polar interactions. Biophysical studies and long-timescale molecular dynamics experiments reveal the mechanisms by which ten point mutations confer a 35,000-fold enhancement in binding affinity, and offer atomic-scale views of the role of conformational dynamics in PD-1/PD-L1 interactions. Finally, we show that the HAC PD-1 exhibits pH-dependent affinity, with pseudo-irreversible binding in a low pH setting akin to the tumor microenvironment. Structure and Dynamics of PD-L1 and an Ultra-High-Affinity PD-1 Receptor Mutant.,Pascolutti R, Sun X, Kao J, Maute RL, Ring AM, Bowman GR, Kruse AC Structure. 2016 Sep 7. pii: S0969-2126(16)30229-5. doi:, 10.1016/j.str.2016.06.026. PMID:27618663[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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