2gtw

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{{Seed}}
 
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[[Image:2gtw.png|left|200px]]
 
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==Human Class I MHC HLA-A2 in complex with the nonameric Melan-A/MART-1(27-35) peptide having A27L substitution==
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The line below this paragraph, containing "STRUCTURE_2gtw", creates the "Structure Box" on the page.
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<StructureSection load='2gtw' size='340' side='right'caption='[[2gtw]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2gtw]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GTW FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.548&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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{{STRUCTURE_2gtw| PDB=2gtw | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gtw OCA], [https://pdbe.org/2gtw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gtw RCSB], [https://www.ebi.ac.uk/pdbsum/2gtw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gtw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/MAR1_HUMAN MAR1_HUMAN] Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the formation of stage II melanosomes.<ref>PMID:15695812</ref> <ref>PMID:19717472</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gt/2gtw_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gtw ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Small structural changes in peptides presented by major histocompatibility complex (MHC) molecules often result in large changes in immunogenicity, supporting the notion that T cell receptors are exquisitely sensitive to antigen structure. Yet there are striking examples of TCR recognition of structurally dissimilar ligands. The resulting unpredictability of how T cells will respond to different or modified antigens impacts both our understanding of the physical bases for TCR specificity as well as efforts to engineer peptides for immunomodulation. In cancer immunotherapy, epitopes and variants derived from the MART-1/Melan-A protein are widely used as clinical vaccines. Two overlapping epitopes spanning amino acid residues 26 through 35 are of particular interest: numerous clinical studies have been performed using variants of the MART-1 26-35 decamer, although only the 27-35 nonamer has been found on the surface of targeted melanoma cells. Here, we show that the 26-35 and 27-35 peptides adopt strikingly different conformations when bound to HLA-A2. Nevertheless, clonally distinct MART-1(26/27-35)-reactive T cells show broad cross-reactivity towards these ligands. Simultaneously, however, many of the cross-reactive T cells remain unable to recognize anchor-modified variants with very subtle structural differences. These dichotomous observations challenge our thinking about how structural information on unligated peptide/MHC complexes should be best used when addressing questions of TCR specificity. Our findings also indicate that caution is warranted in the design of immunotherapeutics based on the MART-1 26/27-35 epitopes, as neither cross-reactivity nor selectivity is predictable based on the analysis of the structures alone.
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===Human Class I MHC HLA-A2 in complex with the nonameric Melan-A/MART-1(27-35) peptide having A27L substitution===
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Structures of MART-126/27-35 Peptide/HLA-A2 complexes reveal a remarkable disconnect between antigen structural homology and T cell recognition.,Borbulevych OY, Insaidoo FK, Baxter TK, Powell DJ Jr, Johnson LA, Restifo NP, Baker BM J Mol Biol. 2007 Oct 5;372(5):1123-36. Epub 2007 Jul 26. PMID:17719062<ref>PMID:17719062</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2gtw" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17719062}}, adds the Publication Abstract to the page
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17719062 is the PubMed ID number.
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*[[MHC 3D structures|MHC 3D structures]]
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*[[MHC I 3D structures|MHC I 3D structures]]
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{{ABSTRACT_PUBMED_17719062}}
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== References ==
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<references/>
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==Disease==
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__TOC__
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Known disease associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Ankylosing spondylitis, susceptibility to, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Stevens-Johnson syndrome, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142800 142800]], Hypoproteinemia, hypercatabolic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109700 109700]]
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</StructureSection>
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==About this Structure==
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2GTW is a 6 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTW OCA].
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==Reference==
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<ref group="xtra">PMID:17719062</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Baker, B M.]]
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[[Category: Large Structures]]
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[[Category: Borbulevych, O Y.]]
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[[Category: Baker BM]]
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[[Category: A27l mutation]]
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[[Category: Borbulevych OY]]
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[[Category: Cancer vaccine]]
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[[Category: Hla-a2]]
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[[Category: Melan-a/mart-1 peptide]]
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[[Category: Melanoma]]
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[[Category: Mhc class i]]
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[[Category: Nonapeptide]]
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[[Category: X-ray crystallography]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 11:19:02 2009''
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Current revision

Human Class I MHC HLA-A2 in complex with the nonameric Melan-A/MART-1(27-35) peptide having A27L substitution

PDB ID 2gtw

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