4jfo: Difference between revisions

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{{STRUCTURE_4jfo|  PDB=4jfo  |  SCENE=  }}
==A2 HLA complex with E1A heteroclitic variant of Melanoma peptide==
===A2 HLA complex with E1A heteroclitic variant of Melanoma peptide===
<StructureSection load='4jfo' size='340' side='right' caption='[[4jfo]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
{{ABSTRACT_PUBMED_23698002}}
== Structural highlights ==
 
<table><tr><td colspan='2'>[[4jfo]] is a 6 chain structure with sequence 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=4JFO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JFO FirstGlance]. <br>
==Disease==
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jfd|4jfd]], [[4jfe|4jfe]], [[4jff|4jff]], [[4jfh|4jfh]], [[4jfp|4jfp]], [[4jfq|4jfq]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA-A, HLAA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4jfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jfo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jfo RCSB], [http://www.ebi.ac.uk/pdbsum/4jfo PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://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>   
[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://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>   
== Function ==
[[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_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 T-cell receptor (TCR) recognises peptides bound to major histocompatibility molecules (pMHC) and allows T-cells to interrogate the cellular proteaome for internal anomalies from the cell surface. The TCR contacts both MHC and peptide in an interaction characterised by weak affinity (KD &gt;1 muM). We used phage-display to produce a melanoma-specific TCR (alpha24beta17) with a &gt;30,000-fold enhanced binding affinity (KD = 600 pM) in order to aid our exploration of the molecular mechanisms utilised to maintain peptide specificity. Remarkably, although the enhanced affinity was mediated primarily through new TCR-MHC contacts, alpha24beta17 remained acutely sensitive to modifications at every position along the peptide backbone, mimicking the specificity of the wild type TCR. Thermodynamic analyses revealed an important role for solvation in directing peptide specificity. These findings advance our understanding of the molecular mechanisms that can govern the exquisite peptide specificity characteristic of TCR recognition.


==Function==
T-cell receptor specificity maintained by altered thermodynamics.,Madura F, Rizkallah PJ, Miles KM, Holland CJ, Bulek AM, Fuller A, Schauenburg AJ, Miles JJ, Liddy N, Sami M, Li Y, Hossain M, Baker BM, Jakobsen BK, Sewell AK, Cole DK J Biol Chem. 2013 May 22. PMID:23698002<ref>PMID:23698002</ref>
[[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4jfo]] is a 6 chain structure with sequence 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=4JFO OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:023698002</ref><references group="xtra"/><references/>
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Baker, B M.]]
[[Category: Baker, B M]]
[[Category: Cole, D K.]]
[[Category: Cole, D K]]
[[Category: Madura, F.]]
[[Category: Madura, F]]
[[Category: Rizkallah, P J.]]
[[Category: Rizkallah, P J]]
[[Category: Sewell, A K.]]
[[Category: Sewell, A K]]
[[Category: High affinity]]
[[Category: High affinity]]
[[Category: Hla]]
[[Category: Hla]]

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