6uz1: Difference between revisions
New page: '''Unreleased structure''' The entry 6uz1 is ON HOLD Authors: Ma, J., Singh, N.K. Description: Noncanonical binding of single-chain A6 TCR variant S3-4 in complex with Tax/HLA-A2 [[Cat... |
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==Noncanonical binding of single-chain A6 TCR variant S3-4 in complex with Tax/HLA-A2== | |||
<StructureSection load='6uz1' size='340' side='right'caption='[[6uz1]], [[Resolution|resolution]] 3.14Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6uz1]] is a 10 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=6UZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UZ1 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]] 3.14Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=6uz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uz1 OCA], [https://pdbe.org/6uz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uz1 RCSB], [https://www.ebi.ac.uk/pdbsum/6uz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uz1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A140T913_HUMAN A0A140T913_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
T cell receptors (TCRs) orchestrate cellular immunity by recognizing peptides presented by a range of major histocompatibility complex (MHC) proteins. Naturally occurring TCRs bind the composite peptide/MHC surface, recognizing peptides that are structurally and chemically compatible with the TCR binding site. Here we describe a molecularly evolved TCR variant that binds the human class I MHC protein HLA-A2 independent of the bound peptide, achieved by a drastic perturbation of the TCR binding geometry that places the molecule far from the peptide binding groove. This unique geometry is unsupportive of normal T cell signaling. A substantial divergence between affinity measurements in solution and in two dimensions between proximal cell membranes leads us to attribute the lack of signaling to steric hindrance that limits binding in the confines of a cell-cell interface. Our results provide an example of how receptor binding geometry can impact T cell function and provide further support for the view that germline-encoded residues in TCR binding loops evolved to drive productive TCR recognition and signaling. | |||
An Engineered T Cell Receptor Variant Realizes the Limits of Functional Binding Modes.,Singh NK, Alonso JA, Harris DT, Anderson SD, Ma J, Hellman LM, Rosenberg AM, Kolawole EM, Evavold BD, Kranz DM, Baker BM Biochemistry. 2020 Oct 19. doi: 10.1021/acs.biochem.0c00689. PMID:33074657<ref>PMID:33074657</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6uz1" style="background-color:#fffaf0;"></div> | ||
[[Category: Ma | |||
==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]] | |||
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ma J]] | |||
[[Category: Singh NK]] | |||
Latest revision as of 14:19, 30 October 2024
Noncanonical binding of single-chain A6 TCR variant S3-4 in complex with Tax/HLA-A2Noncanonical binding of single-chain A6 TCR variant S3-4 in complex with Tax/HLA-A2
Structural highlights
FunctionPublication Abstract from PubMedT cell receptors (TCRs) orchestrate cellular immunity by recognizing peptides presented by a range of major histocompatibility complex (MHC) proteins. Naturally occurring TCRs bind the composite peptide/MHC surface, recognizing peptides that are structurally and chemically compatible with the TCR binding site. Here we describe a molecularly evolved TCR variant that binds the human class I MHC protein HLA-A2 independent of the bound peptide, achieved by a drastic perturbation of the TCR binding geometry that places the molecule far from the peptide binding groove. This unique geometry is unsupportive of normal T cell signaling. A substantial divergence between affinity measurements in solution and in two dimensions between proximal cell membranes leads us to attribute the lack of signaling to steric hindrance that limits binding in the confines of a cell-cell interface. Our results provide an example of how receptor binding geometry can impact T cell function and provide further support for the view that germline-encoded residues in TCR binding loops evolved to drive productive TCR recognition and signaling. An Engineered T Cell Receptor Variant Realizes the Limits of Functional Binding Modes.,Singh NK, Alonso JA, Harris DT, Anderson SD, Ma J, Hellman LM, Rosenberg AM, Kolawole EM, Evavold BD, Kranz DM, Baker BM Biochemistry. 2020 Oct 19. doi: 10.1021/acs.biochem.0c00689. PMID:33074657[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
References
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