View source for 5mzm


==Structure of H-2Db in complex with TEIPP APL Trh4 p3P==
<StructureSection load='5mzm' size='340' side='right'caption='[[5mzm]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mzm]] 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=5MZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MZM 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5mzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mzm OCA], [https://pdbe.org/5mzm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mzm RCSB], [https://www.ebi.ac.uk/pdbsum/5mzm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mzm ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
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== Publication Abstract from PubMed ==
Human cancers frequently display defects in Ag processing and presentation allowing for immune evasion, and they therefore constitute a significant challenge for T cell-based immunotherapy. We have previously demonstrated that the antigenicity of tumor-associated Ags can be significantly enhanced through unconventional residue modifications as a novel tool for MHC class I (MHC-I)-based immunotherapy approaches. We have also previously identified a novel category of cancer neo-epitopes, that is, T cell epitopes associated with impaired peptide processing (TEIPP), that are selectively presented by MHC-I on cells lacking the peptide transporter TAP. In this study, we demonstrate that substitution of the nonanchoring position 3 into a proline residue of the first identified TEIPP peptide, the murine Trh4, results in significantly enhanced recognition by antitumor CTLs toward the wild-type epitope. Although higher immunogenicity has in most cases been associated with increased MHC/peptide complex stability, our results demonstrate that the overall stability of H-2D(b) in complex with the highly immunogenic altered peptide ligand Trh4-p3P is significantly reduced compared with wild-type H-2D(b)/Trh4. Comparison of the crystal structures of the H-2D(b)/Trh4-p3P and H-2D(b)/Trh4 complexes revealed that the conformation of the nonconventional methionine anchor residue p5M is altered, deleting its capacity to form adequate sulfur-pi interactions with H-2D(b) residues, thus reducing the overall longevity of the complex. Collectively, our results indicate that vaccination with Thr4-p3P significantly enhances T cell recognition of targets presenting the wild-type TEIPP epitope and that higher immunogenicity is not necessarily directly related to MHC/peptide complex stability, opening for the possibility to design novel peptide vaccines with reduced MHC/peptide complex stability.

The Immunogenicity of a Proline-Substituted Altered Peptide Ligand toward the Cancer-Associated TEIPP Neoepitope Trh4 Is Unrelated to Complex Stability.,Hafstrand I, Doorduijn EM, Sun R, Talyzina A, Sluijter M, Pellegrino S, Sandalova T, Duru AD, van Hall T, Achour A J Immunol. 2018 Mar 5. pii: jimmunol.1700228. doi: 10.4049/jimmunol.1700228. PMID:29507106<ref>PMID:29507106</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 5mzm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Achour A]]
[[Category: Hafstrand I]]
[[Category: Sandalova T]]