View source for 5e8p


==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]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5e8p]] is a 6 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E8P FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sphingosine_N-acyltransferase Sphingosine N-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.24 2.3.1.24] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5e8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e8p OCA], [http://pdbe.org/5e8p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e8p RCSB], [http://www.ebi.ac.uk/pdbsum/5e8p PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/CERS5_MOUSE CERS5_MOUSE]] Dihydroceramide synthase. Catalyzes the acylation of sphingosine to form dihydroceramide, with high selectivity toward palmitoyl-CoA as acyl donor compared to stearoyl-CoA. Inhibited by fumonisin B1.<ref>PMID:12912983</ref> <ref>PMID:16100120</ref>  [[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5e8p" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Sphingosine N-acyltransferase]]
[[Category: Achour, A]]
[[Category: Buratto, J]]
[[Category: Doorduijn, E]]
[[Category: Duru, A D]]
[[Category: Hafstrand, I]]
[[Category: Hall, T van]]
[[Category: Oliveira, C C]]
[[Category: Sandalova, T]]
[[Category: Cancer]]
[[Category: Immune system]]
[[Category: Mhc-i]]
[[Category: Neo-epitope]]
[[Category: Non-classical peptide binding]]
[[Category: Sulfur-pi interaction]]
[[Category: Tap-deficiency]]
[[Category: Teipp]]