5e8p: Difference between revisions

<StructureSection load='5e8p' size='340' side='right'caption='[[5e8p]], [[Resolution|resolution]] 2.00&Aring;' scene=''>

<table><tr><td colspan='2'>[[5e8p]] is a 6 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=5E8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E8P 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&#8491;</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</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=5e8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e8p OCA], [https://pdbe.org/5e8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e8p RCSB], [https://www.ebi.ac.uk/pdbsum/5e8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e8p ProSAT]</span></td></tr>

[https://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system.

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MHC class I downregulation represents a significant challenge for successful T cell-based immunotherapy. T cell epitopes associated with impaired peptide processing (TEIPP) constitute a novel category of immunogenic Ags that are selectively presented on transporter associated with Ag processing-deficient cells. The TEIPP neoepitopes are CD8 T cell targets, derived from nonmutated self-proteins that might be exploited to prevent immune escape. In this study, the crystal structure of H-2Db in complex with the first identified TEIPP Ag (MCLRMTAVM) derived from the Trh4 protein has been determined to 2.25 A resolution. In contrast to prototypic H-2Db peptides, Trh4 takes a noncanonical peptide-binding pattern with extensive sulfur-pi interactions that contribute to the overall complex stability. Importantly, the noncanonical methionine at peptide position 5 acts as a main anchor, altering only the conformation of the H-2Db residues Y156 and H155 and thereby forming a unique MHC/peptide conformer that is essential for recognition by TEIPP-specific T cells. Substitution of peptide residues p2C and p5M to the conservative alpha-aminobutyric acid and norleucine, respectively, significantly reduced complex stability, without altering peptide conformation or T cell recognition. In contrast, substitution of p5M to a conventional asparagine abolished recognition by the H-2Db/Trh4-specific T cell clone LnB5. We anticipate that the H-2Db/Trh4 complex represents the first example, to our knowledge, of a broader repertoire of alternative MHC class I binders.

 

The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer.,Hafstrand I, Doorduijn EM, Duru AD, Buratto J, Oliveira CC, Sandalova T, van Hall T, Achour A J Immunol. 2016 Jan 22. pii: 1502249. PMID:26800871<ref>PMID:26800871</ref>

 

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 5e8p" style="background-color:#fffaf0;"></div>

 

*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]

[[Category: Large Structures]]

[[Category: Mus musculus]]

[[Category: Achour A]]

[[Category: Buratto J]]

[[Category: Doorduijn E]]

[[Category: Duru AD]]

[[Category: Hafstrand I]]

[[Category: Oliveira CC]]

[[Category: Sandalova T]]

[[Category: Van Hall T]]