View source for 2jcc

==AH3 RECOGNITION OF MUTANT HLA-A2 W167A==
<StructureSection load='2jcc' size='340' side='right' caption='[[2jcc]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jcc]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JCC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JCC FirstGlance]. <br>
</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=2jcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jcc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jcc RCSB], [http://www.ebi.ac.uk/pdbsum/2jcc PDBsum]</span></td></tr>
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== Function ==
[[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] 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/jc/2jcc_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/chain_selection.php?pdb_ID=2ata ConSurf].
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== Publication Abstract from PubMed ==
The keystone of the adaptive immune response is T cell receptor (TCR) recognition of peptide presented by major histocompatibility complex (pMHC) molecules. The crystal structure of AHIII TCR bound to MHC, HLA-A2, showed a large interface with an atypical binding orientation. MHC mutations in the interface of the proteins were tested for changes in TCR recognition. From the range of responses observed, three representative HLA-A2 mutants, T163A, W167A, and K66A, were selected for further study. Binding constants and co-crystal structures of the AHIII TCR and the three mutants were determined. K66 in HLA-A2 makes contacts with both peptide and TCR, and has been identified as a critical residue for recognition by numerous TCR. The K66A mutation resulted in the lowest AHIII T cell response and the lowest binding affinity, which suggests that the T cell response may correlate with affinity. Importantly, the K66A mutation does not affect the conformation of the peptide. The change in affinity appears to be due to a loss in hydrogen bonds in the interface as a result of a conformational change in the TCR complementarity-determining region 3 (CDR3) loop. Isothermal titration calorimetry confirmed the loss of hydrogen bonding by a large loss in enthalpy. Our findings are inconsistent with the notion that the CDR1 and CDR2 loops of the TCR are responsible for MHC restriction, while the CDR3 loops interact solely with the peptide. Instead, we present here an MHC mutation that does not change the conformation of the peptide, yet results in an altered conformation of a CDR3.

Single MHC mutation eliminates enthalpy associated with T cell receptor binding.,Miller PJ, Pazy Y, Conti B, Riddle D, Appella E, Collins EJ J Mol Biol. 2007 Oct 19;373(2):315-27. Epub 2007 Jul 26. PMID:17825839<ref>PMID:17825839</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Beta-2 microglobulin|Beta-2 microglobulin]]
*[[Heat Shock Proteins|Heat Shock Proteins]]
*[[Major histocompatibility complex|Major histocompatibility complex]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Mus musculus]]
[[Category: Benhar, Y P]]
[[Category: Biddison, W]]
[[Category: Collins, E J]]
[[Category: Miller, P]]
[[Category: Class i mhc-tcr co-crystal]]
[[Category: Glycoprotein]]
[[Category: Host-virus interaction]]
[[Category: Hypothetical protein]]
[[Category: Immune response]]
[[Category: Immune system]]
[[Category: Immunoglobulin domain]]
[[Category: Imunoregulatory complex]]
[[Category: Membrane]]
[[Category: Mhc i]]
[[Category: Pyrrolidone carboxylic acid]]
[[Category: Receptor]]
[[Category: Transmembrane]]