4grm: Difference between revisions
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==The crystal structure of the high affinity TCR A6== | |||
===The | <StructureSection load='4grm' size='340' side='right' caption='[[4grm]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4grm]] is a 4 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=4GRM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GRM FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qh3|3qh3]]</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=4grm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4grm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4grm RCSB], [http://www.ebi.ac.uk/pdbsum/4grm PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Natural T cell receptors (TCRs) generally bind to their cognate pMHC molecules with weak affinity and fast kinetics, limiting their use as therapeutic agents. Using phage display, we have engineered a high affinity version of the A6 wild-type TCR (A6wt), specific for the human leukocyte antigen (HLA-A( *)0201) complexed with human T cell lymphotropic virus type 111-19 peptide (A2-Tax). Mutations in just 4 residues in the CDR3beta loop region of the A6wt TCR were selected that improved binding to A2-Tax by nearly 1000-fold. Biophysical measurements of this mutant TCR (A6c134) demonstrated that the enhanced binding was derived through favorable enthalpy and a slower off-rate. The structure of the free A6c134 TCR and the A6c134/A2-Tax complex revealed a native binding mode, similar to the A6wt/A2-Tax complex. However, concordant with the more favorable binding enthalpy, the A6c134 TCR made increased contacts with the Tax peptide compared with the A6wt/A2-Tax complex, demonstrating a peptide-focused mechanism for the enhanced affinity that directly involved the mutated residues in the A6c134 TCR CDR3beta loop. This peptide-focused enhanced TCR binding may represent an important approach for developing antigen specific high affinity TCR reagents for use in T cell based therapies. | |||
Increased Peptide Contacts Govern High Affinity Binding of a Modified TCR Whilst Maintaining a Native pMHC Docking Mode.,Cole DK, Sami M, Scott DR, Rizkallah PJ, Borbulevych OY, Todorov PT, Moysey RK, Jakobsen BK, Boulter JM, Baker BM, Yi Li Front Immunol. 2013 Jun 26;4:168. doi: 10.3389/fimmu.2013.00168. Print 2013. PMID:23805144<ref>PMID:23805144</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Baker, B M | [[Category: Baker, B M]] | ||
[[Category: Borbulevych, O Y | [[Category: Borbulevych, O Y]] | ||
[[Category: Scott, D R | [[Category: Scott, D R]] | ||
[[Category: C134 modification]] | [[Category: C134 modification]] | ||
[[Category: Cross-reactivity]] | [[Category: Cross-reactivity]] | ||
