5txs
From Proteopedia
(Difference between revisions)
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<StructureSection load='5txs' size='340' side='right' caption='[[5txs]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='5txs' size='340' side='right' caption='[[5txs]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5txs]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TXS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TXS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5txs]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TXS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TXS FirstGlance]. <br> |
| - | </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=5txs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txs OCA], [http://pdbe.org/5txs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5txs RCSB], [http://www.ebi.ac.uk/pdbsum/5txs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5txs ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-B, HLAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5txs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txs OCA], [http://pdbe.org/5txs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5txs RCSB], [http://www.ebi.ac.uk/pdbsum/5txs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5txs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/1B15_HUMAN 1B15_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | [[http://www.uniprot.org/uniprot/1B15_HUMAN 1B15_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] 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 == | ||
| + | The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation (ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the X-ray structures of the two peptides bound to HLA-B*15:01 reveals drastically different conformations with measurable changes in the stability of the protein complexes, while the self-epitope is excluded from binding due to steric hindrance in the MHC groove. To evaluate the range of HLA alleles that could display the ALK neoepitopes, we used structure-based Rosetta comparative modeling calculations, which accurately predict several additional high affinity interactions and compare our results with commonly used prediction tools. Subsequent determination of the X-ray structure of an HLA-A*01:01 bound neoepitope validates atomic features seen in our Rosetta models with respect to key residues relevant for MHC stability and T cell receptor recognition. Finally, MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes are recognized by CD8+ T cells. This work provides a rational approach toward high-throughput identification and further optimization of putative neoantigen/HLA targets with desired recognition features for cancer immunotherapy. | ||
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| + | A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations.,Toor JS, Rao AA, McShan AC, Yarmarkovich M, Nerli S, Yamaguchi K, Madejska AA, Nguyen S, Tripathi S, Maris JM, Salama SR, Haussler D, Sgourakis NG Front Immunol. 2018 Jan 30;9:99. doi: 10.3389/fimmu.2018.00099. eCollection 2018. PMID:29441070<ref>PMID:29441070</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5txs" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Haussler, D]] | [[Category: Haussler, D]] | ||
[[Category: Rao, A A]] | [[Category: Rao, A A]] | ||
Revision as of 07:54, 21 March 2018
Crystal structure of an anaplastic lymphoma kinase-derived neuroblastoma tumor antigen bound to the Human Major Histocompatibility Complex Class I molecule HLA-B*1501
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