7l1c: Difference between revisions

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-'''Unreleased structure'''
-The entry 7l1c is ON HOLD  until Paper Publication
+==Crystal structure of HLA-A*03:01 in complex with a mutant PIK3CA peptide==
+<StructureSection load='7l1c' size='340' side='right'caption='[[7l1c]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7l1c]] is a 3 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=7L1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7L1C 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]] 1.96&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7l1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7l1c OCA], [https://pdbe.org/7l1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7l1c RCSB], [https://www.ebi.ac.uk/pdbsum/7l1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7l1c ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Public neoantigens (NeoAgs) represent an elite class of shared cancer-specific epitopes derived from recurrently mutated driver genes. Here we describe a high-throughput platform combining single-cell transcriptomic and T cell receptor (TCR) sequencing to establish whether mutant PIK3CA, among the most frequently genomically altered driver oncogenes, generates an immunogenic public NeoAg. Using this strategy, we developed a panel of TCRs that recognize an endogenously processed neopeptide encompassing a common PIK3CA hotspot mutation restricted by the prevalent human leukocyte antigen (HLA)-A*03:01 allele. Mechanistically, immunogenicity to this public NeoAg arises from enhanced neopeptide/HLA complex stability caused by a preferred HLA anchor substitution. Structural studies indicated that the HLA-bound neopeptide presents a comparatively 'featureless' surface dominated by the peptide's backbone. To bind this epitope with high specificity and affinity, we discovered that a lead TCR clinical candidate engages the neopeptide through an extended interface facilitated by an unusually long CDR3beta loop. In patients with diverse malignancies, we observed NeoAg clonal conservation and spontaneous immunogenicity to the neoepitope. Finally, adoptive transfer of TCR-engineered T cells led to tumor regression in vivo in mice bearing PIK3CA-mutant tumors but not wild-type PIK3CA tumors. Together, these findings establish the immunogenicity and therapeutic potential of a mutant PIK3CA-derived public NeoAg.
-Authors: Ma, J., Baker, B.M.
+Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA.,Chandran SS, Ma J, Klatt MG, Dundar F, Bandlamudi C, Razavi P, Wen HY, Weigelt B, Zumbo P, Fu SN, Banks LB, Yi F, Vercher E, Etxeberria I, Bestman WD, Da Cruz Paula A, Aricescu IS, Drilon A, Betel D, Scheinberg DA, Baker BM, Klebanoff CA Nat Med. 2022 May;28(5):946-957. doi: 10.1038/s41591-022-01786-3. Epub 2022 Apr , 28. PMID:35484264<ref>PMID:35484264</ref>
-Description: Crystal structure of HLA-A*03:01 in complex with a mutant PIK3CA peptide
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Baker, B.M]]
+<div class="pdbe-citations 7l1c" style="background-color:#fffaf0;"></div>
-[[Category: Ma, J]]
+==See Also==
+*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Baker BM]]
+[[Category: Ma J]]