5e8p: Difference between revisions
New page: '''Unreleased structure''' The entry 5e8p is ON HOLD Authors: Hafstrand, I., Doorduijn, E., Duru, A.D., Buratto, J., Oliveira, C.C., Sandalova, T., van Hall, T., Achour, A. Description... |
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The | ==The structure of the TEIPP associated altered peptide ligand Trh4-p5NLE in complex with H-2D(b)== | ||
<StructureSection load='5e8p' size='340' side='right'caption='[[5e8p]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<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]] 2Å</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> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[ | </div> | ||
[[Category: | <div class="pdbe-citations 5e8p" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Achour | ==See Also== | ||
[[Category: Buratto | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | ||
[[Category: | == References == | ||
[[Category: Hafstrand | <references/> | ||
[[Category: Sandalova | __TOC__ | ||
[[Category: Van Hall | </StructureSection> | ||
[[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]] | |||
Latest revision as of 09:17, 5 July 2023
The structure of the TEIPP associated altered peptide ligand Trh4-p5NLE in complex with H-2D(b)The structure of the TEIPP associated altered peptide ligand Trh4-p5NLE in complex with H-2D(b)
Structural highlights
FunctionHA11_MOUSE Involved in the presentation of foreign antigens to the immune system. Publication Abstract from PubMedMHC 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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