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{{STRUCTURE_3bh9|  PDB=3bh9  |  SCENE=  }}
===Crystal Structure of RTY Phosphopeptide Bound to Human Class I MHC HLA-A2===
{{ABSTRACT_PUBMED_18836451}}


==Disease==
==Crystal Structure of RTY Phosphopeptide Bound to Human Class I MHC HLA-A2==
[[http://www.uniprot.org/uniprot/POF1B_HUMAN POF1B_HUMAN]] Defects in POF1B are the cause of premature ovarian failure type 2B (POF2B) [MIM:[http://omim.org/entry/300604 300604]]. An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.<ref>PMID:16773570</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>  
<StructureSection load='3bh9' size='340' side='right'caption='[[3bh9]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bh9]] 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=3BH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BH9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bh9 OCA], [https://pdbe.org/3bh9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bh9 RCSB], [https://www.ebi.ac.uk/pdbsum/3bh9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bh9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/POF1B_HUMAN POF1B_HUMAN] Defects in POF1B are the cause of premature ovarian failure type 2B (POF2B) [MIM:[https://omim.org/entry/300604 300604]. An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.<ref>PMID:16773570</ref>  
== Function ==
[https://www.uniprot.org/uniprot/POF1B_HUMAN POF1B_HUMAN] May be involved in ovary development.<ref>PMID:16773570</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bh/3bh9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=3bh9 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein phosphorylation generates a source of phosphopeptides that are presented by major histocompatibility complex class I molecules and recognized by T cells. As deregulated phosphorylation is a hallmark of malignant transformation, the differential display of phosphopeptides on cancer cells provides an immunological signature of 'transformed self'. Here we demonstrate that phosphorylation can considerably increase peptide binding affinity for HLA-A2. To understand this, we solved crystal structures of four phosphopeptide-HLA-A2 complexes. These identified a novel peptide-binding motif centered on a solvent-exposed phosphate anchor. Our findings indicate that deregulated phosphorylation can create neoantigens by promoting binding to major histocompatibility complex molecules or by affecting the antigenic identity of presented epitopes. These results highlight the potential of phosphopeptides as novel targets for cancer immunotherapy.


==Function==
Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self.,Mohammed F, Cobbold M, Zarling AL, Salim M, Barrett-Wilt GA, Shabanowitz J, Hunt DF, Engelhard VH, Willcox BE Nat Immunol. 2008 Nov;9(11):1236-43. Epub 2008 Oct 5. PMID:18836451<ref>PMID:18836451</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/POF1B_HUMAN POF1B_HUMAN]] May be involved in ovary development.<ref>PMID:16773570</ref> [[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>
[[3bh9]] is a 3 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=3BH9 OCA].
</div>
<div class="pdbe-citations 3bh9" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[Major histocompatibility complex|Major histocompatibility complex]]
*[[MHC 3D structures|MHC 3D structures]]
 
*[[MHC I 3D structures|MHC I 3D structures]]
==Reference==
== References ==
<ref group="xtra">PMID:018836451</ref><references group="xtra"/><references/>
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Barrett-Wilt, G A.]]
[[Category: Large Structures]]
[[Category: Cobbold, M.]]
[[Category: Barrett-Wilt GA]]
[[Category: Engelhard, V H.]]
[[Category: Cobbold M]]
[[Category: Hunt, D F.]]
[[Category: Engelhard VH]]
[[Category: Mohammed, F.]]
[[Category: Hunt DF]]
[[Category: Salim, M.]]
[[Category: Mohammed F]]
[[Category: Shabanowitz, J.]]
[[Category: Salim M]]
[[Category: Willcox, B E.]]
[[Category: Shabanowitz J]]
[[Category: Zarling, A L.]]
[[Category: Willcox BE]]
[[Category: Anchor residue]]
[[Category: Zarling AL]]
[[Category: Glycoprotein]]
[[Category: Hla-a2]]
[[Category: Host-virus interaction]]
[[Category: Immune response]]
[[Category: Immune system]]
[[Category: Immunoglobulin domain]]
[[Category: Mhc]]
[[Category: Mhc i]]
[[Category: Phosphopeptide]]
[[Category: Phosphoprotein]]
[[Category: Phosphoserine]]
[[Category: Transmembrane]]
[[Category: Tumor antigen]]

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