View source for 8wul


==Crystal structure of affinity enhanced TCR in complex with HLA-A*11:01 bound to KRAS-G12V peptide (VVGAVGVGK)==
<StructureSection load='8wul' size='340' side='right'caption='[[8wul]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8wul]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8WUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WUL 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]] 2.36&#8491;</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=8wul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wul OCA], [https://pdbe.org/8wul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wul RCSB], [https://www.ebi.ac.uk/pdbsum/8wul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wul ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Neoantigens derived from somatic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), the most frequently mutated oncogene, represent promising targets for cancer immunotherapy. Recent research highlights the potential role of human leukocyte antigen (HLA) allele A*11:01 in presenting these altered KRAS variants to the immune system. In this study, we successfully generate and identify murine T-cell receptors (TCRs) that specifically recognize KRAS(8-16)(G12V) from three predicted high affinity peptides. By determining the structure of the tumor-specific 4TCR2 bound to KRAS(G12V)-HLA-A*11:01, we conduct structure-based design to create and evaluate TCR variants with markedly enhanced affinity, up to 15.8-fold. This high-affinity TCR mutant, which involved only two amino acid substitutions, display minimal conformational alterations while maintaining a high degree of specificity for the KRAS(G12V) peptide. Our research unveils the molecular mechanisms governing TCR recognition towards KRAS(G12V) neoantigen and yields a range of affinity-enhanced TCR mutants with significant potential for immunotherapy strategies targeting tumors harboring the KRAS(G12V) mutation.

Identification and affinity enhancement of T-cell receptor targeting a KRAS(G12V) cancer neoantigen.,Zhang M, Xu W, Luo L, Guan F, Wang X, Zhu P, Zhang J, Zhou X, Wang F, Ye S Commun Biol. 2024 Apr 29;7(1):512. doi: 10.1038/s42003-024-06209-2. PMID:38684865<ref>PMID:38684865</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8wul" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Guan FH]]
[[Category: Luo LJ]]
[[Category: Wang F]]
[[Category: Wang XY]]
[[Category: Xu W]]
[[Category: Ye S]]
[[Category: Zhang JH]]
[[Category: Zhang MY]]
[[Category: Zhou XY]]
[[Category: Zhu P]]