6sru
From Proteopedia
(Difference between revisions)
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==Structure of Ig-like V-type domian of mouse Programmed cell death 1 ligand 1 (PD-L1)== | ==Structure of Ig-like V-type domian of mouse Programmed cell death 1 ligand 1 (PD-L1)== | ||
| - | <StructureSection load='6sru' size='340' side='right'caption='[[6sru]]' scene=''> | + | <StructureSection load='6sru' size='340' side='right'caption='[[6sru]], [[Resolution|resolution]] 2.53Å' 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=6SRU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SRU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6sru]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SRU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SRU 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=6sru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sru OCA], [https://pdbe.org/6sru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sru RCSB], [https://www.ebi.ac.uk/pdbsum/6sru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sru 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]] 2.532Å</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=6sru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sru OCA], [https://pdbe.org/6sru PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sru RCSB], [https://www.ebi.ac.uk/pdbsum/6sru PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sru ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PD1L1_MOUSE PD1L1_MOUSE] Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11238124). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11238124). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:11015443, PubMed:12719480).<ref>PMID:11015443</ref> <ref>PMID:11238124</ref> <ref>PMID:12719480</ref> The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:12218188, PubMed:27281199). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (PubMed:12218188). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (PubMed:12218188).<ref>PMID:12218188</ref> <ref>PMID:27281199</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In the development of PD-L1-blocking therapeutics, it is essential to transfer initial in vitro findings into proper in vivo animal models. Classical immunocompetent mice are attractive due to high accessibility and low experimental costs. However, it is unknown whether inter-species differences in PD-L1 sequence and structure would allow for human-mouse cross applications. Here, we disclose the first structure of the mouse (m) PD-L1 and analyze its similarity to the human (h) PD-L1. We show that mPD-L1 interacts with hPD-1 and provides a negative signal toward activated Jurkat T cells. We also show major differences in druggability between the hPD-L1 and mPD-L1 using therapeutic antibodies, a macrocyclic peptide, and small molecules. Our study indicates that while the amino acid sequence is well conserved between the hPD-L1 and mPD-L1 and overall structures are almost identical, crucial differences determine the interaction with anti-PD-L1 agents, that cannot be easily predicted in silico. | ||
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| + | Human and mouse PD-L1: similar molecular structure, but different druggability profiles.,Magiera-Mularz K, Kocik J, Musielak B, Plewka J, Sala D, Machula M, Grudnik P, Hajduk M, Czepiel M, Siedlar M, Holak TA, Skalniak L iScience. 2020 Dec 24;24(1):101960. doi: 10.1016/j.isci.2020.101960. eCollection , 2021 Jan 22. PMID:33437940<ref>PMID:33437940</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6sru" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
[[Category: Grudnik P]] | [[Category: Grudnik P]] | ||
[[Category: Holak TA]] | [[Category: Holak TA]] | ||
[[Category: Magiera-Mularz K]] | [[Category: Magiera-Mularz K]] | ||
[[Category: Sala D]] | [[Category: Sala D]] | ||
Revision as of 12:46, 24 January 2024
Structure of Ig-like V-type domian of mouse Programmed cell death 1 ligand 1 (PD-L1)
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