View source for 5jds


==Crystal structure of PD-L1 complexed with a nanobody at 1.7 Angstron resolution==
<StructureSection load='5jds' size='340' side='right'caption='[[5jds]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jds]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelidae Camelidae] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JDS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JDS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</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>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5jds FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jds OCA], [https://pdbe.org/5jds PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jds RCSB], [https://www.ebi.ac.uk/pdbsum/5jds PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jds ProSAT]</span></td></tr>
</table>
== Function ==
[https://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 use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 A resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids. This loop forms two short helices and develops key hydrophobic and ionic interactions with PD-L1 residues, such as Ile54, Tyr56 and Arg113, which are also involved in PD-1 binding. The detailed mutagenesis study identified the hotspot residues of the PD-L1 surface and provides an explanation for the stronger (~1 000-fold) binding of KN035 to PD-L1 than PD-1 and its lack of binding to PD-L2. Overall, this study reveals how a single immunoglobulin-variable scaffold of KN035 or PD-1 can bind to a flat protein surface through either a single surface loop or beta-sheet strands; and provides a basis for designing new immune checkpoint blockers and generating bi-specific antibodies for combination therapy.

Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade.,Zhang F, Wei H, Wang X, Bai Y, Wang P, Wu J, Jiang X, Wang Y, Cai H, Xu T, Zhou A Cell Discov. 2017 Mar 7;3:17004. doi: 10.1038/celldisc.2017.4. eCollection 2017. PMID:28280600<ref>PMID:28280600</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5jds" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Camelidae]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wei H]]
[[Category: Zhou A]]