View source for 9wk0


==Neoantigen Rac1P29S-HLA-A2==
<StructureSection load='9wk0' size='340' side='right'caption='[[9wk0]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wk0]] 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=9WK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WK0 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]] 1.8&#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=9wk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wk0 OCA], [https://pdbe.org/9wk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wk0 RCSB], [https://www.ebi.ac.uk/pdbsum/9wk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wk0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8WLS4_HUMAN Q8WLS4_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
T cell receptor (TCR)-based immunotherapy can drive cancer regression by targeting neoantigens derived from mutations in self-proteins. Most neoantigens result from mutations in solvent-exposed residues creating neoepitopes that allow highly specific TCR recognition. Here, we describe a melanoma neoantigen (Rac1(P29S)) caused by a mutation at a primary anchor residue. Unlike typical cases, the immunogenicity of Rac1(P29S) stems from this anchor mutation, which permits MHC presentation of the mutant peptide but not the wild-type counterpart. We determined the structures of both the mutant Rac1(P29S)-HLA-A2 complex and its complex with the tumor-specific TCR 5934. These structures show how the P29S mutation makes a Rac1 self- peptide visible to T cells. Notably, TCR 5934 primarily engages the C-terminal, non-mutated P8 threonine residue of Rac1(P29S) -far from the N-terminal mutated P2 serine. This contrasts with most neoantigen-specific TCRs, which typically focus on the mutated residue to distinguish mutant from wild-type peptides. Together, these findings provide a structural framework to guide the development of TCR-based cancer immunotherapies.

Structural basis for TCR recognition of a Rac1 neoantigen arising from anchor residue mutation.,Zeng Y, Yang D, Zhao J, Yuan P, Jin H, Liao W, Chen G, Wu D J Struct Biol. 2026 May 25;218(3):108329. doi: 10.1016/j.jsb.2026.108329. PMID:42190883<ref>PMID:42190883</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9wk0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wu DC]]
[[Category: Yang DD]]