2fo4

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{{STRUCTURE_2fo4| PDB=2fo4 | SCENE= }}
 
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===Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide===
 
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{{ABSTRACT_PUBMED_17067310}}
 
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==Disease==
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==Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide==
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[[http://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN]] Note=MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes.
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<StructureSection load='2fo4' size='340' side='right'caption='[[2fo4]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2fo4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FO4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FO4 FirstGlance]. <br>
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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]] 2.7&#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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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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=2fo4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fo4 OCA], [https://pdbe.org/2fo4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fo4 RCSB], [https://www.ebi.ac.uk/pdbsum/2fo4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fo4 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q3UBW0_MOUSE Q3UBW0_MOUSE] Involved in the presentation of foreign antigens to the immune system.[ARBA:ARBA00002297]
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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/fo/2fo4_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=2fo4 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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Designing peptide-based vaccines for therapeutic applications in cancer immunotherapy requires detailed knowledge of the interactions between the antigenic peptide and major histocompatibility complex (MHC) in addition to that between the peptide-MHC complex and the T-cell receptor. Past efforts to immunize with high-affinity tumour-associated antigenic peptides have not been very immunogenic, which may be attributed to the lack of T cells to these peptides, having been deleted during thymic development. For this reason, low-to-medium affinity non-canonical peptides represent more suitable candidates. However, in addition to the difficulty in identifying such antigens, peptide binding to MHC, and hence its ability to induce a strong immune response, is limited. Therefore, to enhance binding to MHC and improve immune responses, anchor modifications of non-canonical tumour-associated peptides would be advantageous. In this study, the non-canonical tumour-associated peptide from MUC1, MUC1-8 (SAPDTRPA), was modified at the MHC anchor residues to SAPDFRPL (MUC1-8-5F8L) and showed enhanced binding to H-2Kb and improved immune responses. Furthermore, the crystal structure of MUC1-8-5F8L in complex with H-2Kb was determined and it revealed that binding of the peptide to MHC is similar to that of the canonical peptide OVA8 (SIINFEKL).
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==Function==
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Enhanced major histocompatibility complex class I binding and immune responses through anchor modification of the non-canonical tumour-associated mucin 1-8 peptide.,Lazoura E, Lodding J, Farrugia W, Ramsland PA, Stevens J, Wilson IA, Pietersz GA, Apostolopoulos V Immunology. 2006 Nov;119(3):306-16. PMID:17067310<ref>PMID:17067310</ref>
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[[http://www.uniprot.org/uniprot/HA1B_MOUSE HA1B_MOUSE]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/MUC1_HUMAN MUC1_HUMAN]] The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.<ref>PMID:9139698</ref><ref>PMID:11877440</ref><ref>PMID:14688481</ref><ref>PMID:15710329</ref><ref>PMID:16288032</ref><ref>PMID:15513966</ref><ref>PMID:17524503</ref><ref>PMID:17308127</ref><ref>PMID:16983337</ref> The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, SRC and NF-kappa-B pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Promotes tumor progression. Regulates TP53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of TP53 and represses TP53 activity.<ref>PMID:9139698</ref><ref>PMID:11877440</ref><ref>PMID:14688481</ref><ref>PMID:15710329</ref><ref>PMID:16288032</ref><ref>PMID:15513966</ref><ref>PMID:17524503</ref><ref>PMID:17308127</ref><ref>PMID:16983337</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.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[2fo4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FO4 OCA].
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</div>
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<div class="pdbe-citations 2fo4" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Beta-2 microglobulin|Beta-2 microglobulin]]
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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*[[Major histocompatibility complex|Major histocompatibility complex]]
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:017067310</ref><references group="xtra"/><references/>
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Lazoura, E.]]
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[[Category: Lazoura E]]
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[[Category: Ramsland, P A.]]
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[[Category: Ramsland PA]]
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[[Category: Anchor modification]]
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[[Category: H-2kb]]
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[[Category: Immune system]]
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[[Category: Muc1]]
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[[Category: Muc1-8]]
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[[Category: Non-canonical peptide]]
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[[Category: Vaccine design]]
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Current revision

Enhanced MHC class I binding and immune responses through anchor modification of the non-canonical tumor associated MUC1-8 peptide

PDB ID 2fo4

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