5ius: Difference between revisions
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==Crystal structure of human PD-L1 in complex with high affinity PD-1 mutant== | ==Crystal structure of human PD-L1 in complex with high affinity PD-1 mutant== | ||
<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. 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 [http:// | <table><tr><td colspan='2'>[[5ius]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=5IUS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | </td></tr><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'>[http:// | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDCD1, PD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CD274, B7H1, PDCD1L1, PDCD1LG1, PDL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5ius FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ius OCA], [http://pdbe.org/5ius PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ius RCSB], [http://www.ebi.ac.uk/pdbsum/5ius PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ius ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5ius" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5ius" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Cell death protein|Cell death protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Bowman, G R]] | [[Category: Bowman, G R]] | ||
[[Category: Kao, J]] | [[Category: Kao, J]] | ||
Revision as of 10:32, 3 June 2020
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
Disease[PDCD1_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] Function[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.[2] [PD1L1_HUMAN] Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.[3] [4] 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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