View source for 5ius


==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]] 2.89&Aring;' scene=''>
== Structural highlights ==
<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" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
<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>
== Disease ==
[[http://www.uniprot.org/uniprot/PDCD1_HUMAN PDCD1_HUMAN]] Systemic lupus erythematosus;Multiple sclerosis. Systemic lupus erythematosus 2 (SLEB2) [MIM:[http://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 ==
[[http://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>  [[http://www.uniprot.org/uniprot/PD1L1_HUMAN 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.<ref>PMID:10581077</ref> <ref>PMID:11015443</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 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<ref>PMID:27618663</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ius" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cell death protein|Cell death protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Bowman, G R]]
[[Category: Kao, J]]
[[Category: Kruse, A C]]
[[Category: Maute, R]]
[[Category: Pascolutti, R]]
[[Category: Ring, A M]]
[[Category: Sun, X]]
[[Category: Cancer]]
[[Category: Immune checkpoint]]
[[Category: Immune system]]
[[Category: Receptor]]
[[Category: Tumor surveillance]]