1s9w

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{{Seed}}
 
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[[Image:1s9w.png|left|200px]]
 
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==Crystal Structure Analysis of NY-ESO-1 epitope, SLLMWITQC, in complex with HLA-A2==
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The line below this paragraph, containing "STRUCTURE_1s9w", creates the "Structure Box" on the page.
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<StructureSection load='1s9w' size='340' side='right'caption='[[1s9w]], [[Resolution|resolution]] 2.20&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'>[[1s9w]] is a 3 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=1S9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S9W 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]] 2.2&#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=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_1s9w| PDB=1s9w | 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=1s9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s9w OCA], [https://pdbe.org/1s9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s9w RCSB], [https://www.ebi.ac.uk/pdbsum/1s9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s9w ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://omim.org/entry/241600 241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
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== Function ==
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[https://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.
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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/s9/1s9w_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1s9w 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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NY-ESO-1, a commonly expressed tumor antigen of the cancer-testis family, is expressed by a wide range of tumors but not found in normal adult somatic tissue, making it an ideal cancer vaccine candidate. Peptides derived from NY-ESO-1 have shown preclinical and clinical trial promise; however, biochemical features of these peptides have complicated their formulation and led to heterogeneous immune responses. We have taken a rational approach to engineer an HLA A2-restricted NY-ESO-1-derived T cell epitope with improved formulation and immunogenicity to the wild type peptide. To accomplish this, we have solved the x-ray crystallographic structures of HLA A2 complexed to NY-ESO (157-165) and two analogues of this peptide in which the C-terminal cysteine residue has been substituted to alanine or serine. Substitution of cysteine by serine maintained peptide conformation yet reduced complex stability, resulting in poor cytotoxic T lymphocyte recognition. Conversely, substitution with alanine maintained complex stability and cytotoxic T lymphocyte recognition. Based on the structures of the three HLA A2 complexes, we incorporated 2-aminoisobutyric acid, an isostereomer of cysteine, into the epitope. This analogue is impervious to oxidative damage, cysteinylation, and dimerization of the peptide epitope upon formulation that is characteristic of the wild type peptide. Therefore, this approach has yielded a potential therapeutic molecule that satiates the hydrophobic F pocket of HLA A2 and exhibited superior immunogenicity relative to the wild type peptide.
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===Crystal Structure Analysis of NY-ESO-1 epitope, SLLMWITQC, in complex with HLA-A2===
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Functional and structural characteristics of NY-ESO-1-related HLA A2-restricted epitopes and the design of a novel immunogenic analogue.,Webb AI, Dunstone MA, Chen W, Aguilar MI, Chen Q, Jackson H, Chang L, Kjer-Nielsen L, Beddoe T, McCluskey J, Rossjohn J, Purcell AW J Biol Chem. 2004 May 28;279(22):23438-46. Epub 2004 Mar 5. PMID:15004033<ref>PMID:15004033</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 1s9w" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15004033}}, 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 15004033 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_15004033}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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1S9W is a [[Protein complex]] 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=1S9W OCA].
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</StructureSection>
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==Reference==
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Functional and structural characteristics of NY-ESO-1-related HLA A2-restricted epitopes and the design of a novel immunogenic analogue., Webb AI, Dunstone MA, Chen W, Aguilar MI, Chen Q, Jackson H, Chang L, Kjer-Nielsen L, Beddoe T, McCluskey J, Rossjohn J, Purcell AW, J Biol Chem. 2004 May 28;279(22):23438-46. Epub 2004 Mar 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15004033 15004033]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Aguilar, M I.]]
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[[Category: Aguilar MI]]
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[[Category: Beddoe, T.]]
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[[Category: Beddoe T]]
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[[Category: Chang, L.]]
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[[Category: Chang L]]
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[[Category: Chen, Q.]]
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[[Category: Chen Q]]
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[[Category: Chen, W.]]
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[[Category: Chen W]]
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[[Category: Dunstone, M A.]]
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[[Category: Dunstone MA]]
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[[Category: Kjer-Nielsen, L.]]
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[[Category: Kjer-Nielsen L]]
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[[Category: McCluskey, J.]]
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[[Category: McCluskey J]]
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[[Category: Purcell, A W.]]
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[[Category: Purcell AW]]
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[[Category: Rossjohn, J.]]
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[[Category: Rossjohn J]]
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[[Category: Webb, A I.]]
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[[Category: Webb AI]]
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[[Category: Immune system]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:38:02 2008''
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Current revision

Crystal Structure Analysis of NY-ESO-1 epitope, SLLMWITQC, in complex with HLA-A2

PDB ID 1s9w

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