2clv: Difference between revisions

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New page: left|200px<br /><applet load="2clv" size="450" color="white" frame="true" align="right" spinBox="true" caption="2clv, resolution 1.90Å" /> '''MHC CLASS I NATURAL ...
 
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[[Image:2clv.gif|left|200px]]<br /><applet load="2clv" size="450" color="white" frame="true" align="right" spinBox="true"
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'''MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM8 PEPTIDE'''<br />


==Overview==
==MHC Class I Natural Mutant H-2Kbm8 Heavy Chain Complexed With beta-2 Microglobulin and pBM8 peptide==
We have characterized three different programs of activation for, alloreactive CD8 T cells expressing the BM3.3 TCR, their elicitation, depending on the characteristics of the stimulating peptide/MHC complex., The high-affinity interaction between the TCR and the K(b)-associated, endogenous peptide pBM1 (INFDFNTI) induced a complete differentiation, program into effector cells correlated with sustained ERK activation. The, K(bm8) variant elicited a partial activation program with delayed T cell, proliferation, poor CTL activity and undetectable ERK phosphorylation;, this resulted from a low-avidity interaction of TCR BM3.3 with a newly, identified endogenous peptide, pBM8 (SQYYYNSL). Interestingly, mismatched, pBM1/K(bm8) complexes induced a split response in BM3.3 T cells, with, total reconstitution of T cell proliferation but defective generation of, CTL activity that was correlated with strong but shortened ERK, phosphorylation. Crystal structures highlight the molecular basis for the, higher stability of pBM8/K(bm8) compared to pBM1/K(bm8) complexes that, exist in two conformers. This study illustrates the importance of the, stability of both peptide/MHC and peptide/MHC-TCR interactions for, induction of sustained signaling required to induce optimal CTL effector, functions. Subtle allelic structural variations, amplified by peptide, selection, may thus orient distinct outcomes of alloreactive TCR-based, therapies.
<StructureSection load='2clv' size='340' side='right'caption='[[2clv]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2clv]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CLV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CLV 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]] 1.9&#8491;</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=2clv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2clv OCA], [https://pdbe.org/2clv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2clv RCSB], [https://www.ebi.ac.uk/pdbsum/2clv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2clv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HA1B_MOUSE HA1B_MOUSE] Involved in the presentation of foreign 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/cl/2clv_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=2clv ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have characterized three different programs of activation for alloreactive CD8 T cells expressing the BM3.3 TCR, their elicitation depending on the characteristics of the stimulating peptide/MHC complex. The high-affinity interaction between the TCR and the K(b)-associated endogenous peptide pBM1 (INFDFNTI) induced a complete differentiation program into effector cells correlated with sustained ERK activation. The K(bm8) variant elicited a partial activation program with delayed T cell proliferation, poor CTL activity and undetectable ERK phosphorylation; this resulted from a low-avidity interaction of TCR BM3.3 with a newly identified endogenous peptide, pBM8 (SQYYYNSL). Interestingly, mismatched pBM1/K(bm8) complexes induced a split response in BM3.3 T cells, with total reconstitution of T cell proliferation but defective generation of CTL activity that was correlated with strong but shortened ERK phosphorylation. Crystal structures highlight the molecular basis for the higher stability of pBM8/K(bm8) compared to pBM1/K(bm8) complexes that exist in two conformers. This study illustrates the importance of the stability of both peptide/MHC and peptide/MHC-TCR interactions for induction of sustained signaling required to induce optimal CTL effector functions. Subtle allelic structural variations, amplified by peptide selection, may thus orient distinct outcomes of alloreactive TCR-based therapies.


==About this Structure==
Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes.,Auphan-Anezin N, Mazza C, Guimezanes A, Barrett-Wilt GA, Montero-Julian F, Roussel A, Hunt DF, Malissen B, Schmitt-Verhulst AM Eur J Immunol. 2006 Jul;36(7):1856-66. PMID:16761314<ref>PMID:16761314</ref>
2CLV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CLV OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes., Auphan-Anezin N, Mazza C, Guimezanes A, Barrett-Wilt GA, Montero-Julian F, Roussel A, Hunt DF, Malissen B, Schmitt-Verhulst AM, Eur J Immunol. 2006 Jul;36(7):1856-66. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16761314 16761314]
</div>
<div class="pdbe-citations 2clv" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
*[[MHC 3D structures|MHC 3D structures]]
*[[MHC I 3D structures|MHC I 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Auphan-Anezin N]]
[[Category: Auphan-Anezin, N.]]
[[Category: Barrett-Wilt GA]]
[[Category: Barrett-Wilt, G.A.]]
[[Category: Guimezanes A]]
[[Category: Guimezanes, A.]]
[[Category: Hunt DF]]
[[Category: Hunt, D.F.]]
[[Category: Malissen B]]
[[Category: Malissen, B.]]
[[Category: Mazza C]]
[[Category: Mazza, C.]]
[[Category: Montero-Julian F]]
[[Category: Montero-Julian, F.]]
[[Category: Roussel A]]
[[Category: Roussel, A.]]
[[Category: Schmitt-Verhulst AM]]
[[Category: Schmitt-Verhulst, A.M.]]
[[Category: alloreactivity]]
[[Category: class i mhc]]
[[Category: glycoprotein]]
[[Category: h-2kbm8]]
[[Category: immune response]]
[[Category: immune system]]
[[Category: immunoglobulin domain]]
[[Category: membrane]]
[[Category: mhc i]]
[[Category: polymorphism]]
[[Category: transmembrane]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 09:09:55 2007''

Latest revision as of 09:04, 6 November 2024

MHC Class I Natural Mutant H-2Kbm8 Heavy Chain Complexed With beta-2 Microglobulin and pBM8 peptide

2clv, resolution 1.90Å

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