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==== | ==Crystal structure of InhA:01 TCR in complex with HLA-E (Y84C) bound to InhA (53-61 GCG)== | ||
<StructureSection load='6zkx' size='340' side='right'caption='[[6zkx]]' scene=''> | <StructureSection load='6zkx' size='340' side='right'caption='[[6zkx]], [[Resolution|resolution]] 2.17Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[6zkx]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZKX FirstGlance]. <br> | ||
</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=6zkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zkx OCA], [https://pdbe.org/6zkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zkx RCSB], [https://www.ebi.ac.uk/pdbsum/6zkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zkx ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.17Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6zkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zkx OCA], [https://pdbe.org/6zkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zkx RCSB], [https://www.ebi.ac.uk/pdbsum/6zkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zkx ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/HLAE_HUMAN HLAE_HUMAN] Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs. | |||
Structure-guided stabilization of pathogen-derived peptide-HLA-E complexes using non-natural amino acids conserves native TCR recognition.,Barber C, De Souza VA, Paterson RL, Martin-Urdiroz M, Mulakkal NC, Srikannathasan V, Connolly M, Phillips G, Foong-Leong T, Pengelly R, Karuppiah V, Grant T, Dembek M, Verma A, Gibbs-Howe D, Blicher TH, Knox A, Robinson RA, Cole DK, Leonard S Eur J Immunol. 2022 Apr;52(4):618-632. doi: 10.1002/eji.202149745. Epub 2022 Feb , 13. PMID:35108401<ref>PMID:35108401</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6zkx" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Karuppiah V]] | |||
[[Category: Robinson RA]] | |||
[[Category: Srikannathasan V]] | |||
Latest revision as of 14:53, 1 February 2024
Crystal structure of InhA:01 TCR in complex with HLA-E (Y84C) bound to InhA (53-61 GCG)Crystal structure of InhA:01 TCR in complex with HLA-E (Y84C) bound to InhA (53-61 GCG)
Structural highlights
FunctionHLAE_HUMAN Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. Publication Abstract from PubMedThe nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs. Structure-guided stabilization of pathogen-derived peptide-HLA-E complexes using non-natural amino acids conserves native TCR recognition.,Barber C, De Souza VA, Paterson RL, Martin-Urdiroz M, Mulakkal NC, Srikannathasan V, Connolly M, Phillips G, Foong-Leong T, Pengelly R, Karuppiah V, Grant T, Dembek M, Verma A, Gibbs-Howe D, Blicher TH, Knox A, Robinson RA, Cole DK, Leonard S Eur J Immunol. 2022 Apr;52(4):618-632. doi: 10.1002/eji.202149745. Epub 2022 Feb , 13. PMID:35108401[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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