View source for 3gsx


==Crystal structure of the binary complex between HLA-A2 and HCMV NLV-T8V peptide variant==
<StructureSection load='3gsx' size='340' side='right'caption='[[3gsx]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gsx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GSX FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3gsn|3gsn]], [[3gso|3gso]], [[3gsq|3gsq]], [[3gsr|3gsr]], [[3gsu|3gsu]], [[3gsv|3gsv]], [[3gsw|3gsw]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HLA, HLA-A, HLAA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), B2M, Beta-2 microglubulin, CDABP0092, HDCMA22P ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3gsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gsx OCA], [https://pdbe.org/3gsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gsx RCSB], [https://www.ebi.ac.uk/pdbsum/3gsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gsx ProSAT]</span></td></tr>
</table>
== Disease ==
[[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>  
== Function ==
[[https://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[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. 
== 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/gs/3gsx_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3gsx ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 T cell clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these public T cell responses, we have performed structural, biophysical, and functional analyses of an immunodominant public TCR (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65(495-503)) and selected in vivo from a diverse repertoire after chronic stimulations. Unlike the two immunodominant public TCRs crystallized so far, which focused on one peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of available peptide residues. The conservation of some peptide-MHC complex-contacting amino acids by lower-affinity TCRs suggests a shared TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal Ag-specific response after repeated viral stimulations is based on a receptor displaying a high structural complementarity with the entire peptide and focusing on three peptide hotspots. This highlights key parameters underlying the selection of a protective T cell response against HCMV infection, which remains a major health issue in patients undergoing bone marrow transplantation.

Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope.,Gras S, Saulquin X, Reiser JB, Debeaupuis E, Echasserieau K, Kissenpfennig A, Legoux F, Chouquet A, Le Gorrec M, Machillot P, Neveu B, Thielens N, Malissen B, Bonneville M, Housset D J Immunol. 2009 Jul 1;183(1):430-7. PMID:19542454<ref>PMID:19542454</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3gsx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[MHC 3D structures|MHC 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Bonneville, M]]
[[Category: Chouquet, A]]
[[Category: Debeaupuis, E]]
[[Category: Echasserieau, K]]
[[Category: Gorrec, M Le]]
[[Category: Gras, S]]
[[Category: Housset, D]]
[[Category: Kissenpfennig, A]]
[[Category: Legoux, F]]
[[Category: Machillot, P]]
[[Category: Malissen, B]]
[[Category: Neveu, B]]
[[Category: Reiser, J B]]
[[Category: Saulquin, X]]
[[Category: Thielens, N]]
[[Category: Hla]]
[[Category: Host-virus interaction]]
[[Category: Human cytomegalovirus]]
[[Category: Immune response]]
[[Category: Immune system]]
[[Category: Immunodominance]]
[[Category: Immunoglobulin domain]]
[[Category: Membrane]]
[[Category: Mhc i]]
[[Category: Polymorphism]]
[[Category: Pp65]]
[[Category: Public response]]
[[Category: Restrained response]]