6bj2: Difference between revisions

<StructureSection load='6bj2' size='340' side='right'caption='[[6bj2]], [[Resolution|resolution]] 3.35&Aring;' scene=''>

<table><tr><td colspan='2'>[[6bj2]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BJ2 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]] 3.35&#8491;</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6bj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bj2 OCA], [https://pdbe.org/6bj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bj2 RCSB], [https://www.ebi.ac.uk/pdbsum/6bj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bj2 ProSAT]</span></td></tr>

[https://www.uniprot.org/uniprot/Q6IRV4_HUMAN Q6IRV4_HUMAN]  

TCR-signaling strength generally correlates with peptide-MHC binding affinity; however, exceptions exist. We find high-affinity, yet non-stimulatory, interactions occur with high frequency in the human T cell repertoire. Here, we studied human TCRs that are refractory to activation by pMHC ligands despite robust binding. Analysis of 3D affinity, 2D dwell time, and crystal structures of stimulatory versus non-stimulatory TCR-pMHC interactions failed to account for their different signaling outcomes. Using yeast pMHC display, we identified peptide agonists of a formerly non-responsive TCR. Single-molecule force measurements demonstrated the emergence of catch bonds in the activating TCR-pMHC interactions, correlating with exclusion of CD45 from the TCR-APC contact site. Molecular dynamics simulations of TCR-pMHC disengagement distinguished agonist from non-agonist ligands based on the acquisition of catch bonds within the TCR-pMHC interface. The isolation of catch bonds as a parameter mediating the coupling of TCR binding and signaling has important implications for TCR and antigen engineering for immunotherapy.

 

Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding.,Sibener LV, Fernandes RA, Kolawole EM, Carbone CB, Liu F, McAffee D, Birnbaum ME, Yang X, Su LF, Yu W, Dong S, Gee MH, Jude KM, Davis MM, Groves JT, Goddard WA 3rd, Heath JR, Evavold BD, Vale RD, Garcia KC Cell. 2018 Jul 26;174(3):672-687.e27. doi: 10.1016/j.cell.2018.06.017. PMID:30053426<ref>PMID:30053426</ref>

 

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 6bj2" style="background-color:#fffaf0;"></div>

 

*[[T-cell receptor 3D structures|T-cell receptor 3D structures]]

[[Category: Homo sapiens]]

[[Category: Human immunodeficiency virus 1]]

[[Category: Large Structures]]

[[Category: Garcia KC]]

[[Category: Jude KM]]

[[Category: Sibener LV]]