8shi: Difference between revisions
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==Valpha3S1 Vbeta13S1 HLA C 0602 VRSRRCLRL== | |||
<StructureSection load='8shi' size='340' side='right'caption='[[8shi]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8shi]] 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=8SHI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SHI 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]] 2.9000173Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</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=8shi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8shi OCA], [https://pdbe.org/8shi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8shi RCSB], [https://www.ebi.ac.uk/pdbsum/8shi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8shi ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/F6IQM2_HUMAN F6IQM2_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Psoriasis is a chronic skin disease characterised by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the Human Leukocyte antigen (HLA) C*06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Valpha3S1/Vbeta13S1) isolated from psoriatic plaques is selective for HLA-C*06:02-presenting a peptide derived from the melanocyte-specific auto-antigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR-HLA-C*06:02- ADAMTSL5 complex with a stabilised peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C*06:02 alpha1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide binding groove of HLA C*06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognised by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis, while simultaneously expanding our knowledge of how TCRs engage HLA-C. | |||
Complimentary electrostatics dominate T Cell Receptor binding to a psoriasis-associated-peptide-antigen presented by Human Leukocyte Antigen (HLA) C*06:02.,Anand S, Littler DR, Mobbs JI, Braun A, Baker DG, Tennant L, Purcell AW, Vivian JP, Rossjohn J J Biol Chem. 2023 Jun 15:104930. doi: 10.1016/j.jbc.2023.104930. PMID:37330172<ref>PMID:37330172</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Anand | <div class="pdbe-citations 8shi" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Anand S]] | |||
[[Category: Littler DR]] | |||
[[Category: Rossjohn J]] | |||
[[Category: Vivian JP]] | |||
Latest revision as of 00:22, 29 June 2023
Valpha3S1 Vbeta13S1 HLA C 0602 VRSRRCLRLValpha3S1 Vbeta13S1 HLA C 0602 VRSRRCLRL
Structural highlights
FunctionPublication Abstract from PubMedPsoriasis is a chronic skin disease characterised by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the Human Leukocyte antigen (HLA) C*06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Valpha3S1/Vbeta13S1) isolated from psoriatic plaques is selective for HLA-C*06:02-presenting a peptide derived from the melanocyte-specific auto-antigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR-HLA-C*06:02- ADAMTSL5 complex with a stabilised peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C*06:02 alpha1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide binding groove of HLA C*06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognised by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis, while simultaneously expanding our knowledge of how TCRs engage HLA-C. Complimentary electrostatics dominate T Cell Receptor binding to a psoriasis-associated-peptide-antigen presented by Human Leukocyte Antigen (HLA) C*06:02.,Anand S, Littler DR, Mobbs JI, Braun A, Baker DG, Tennant L, Purcell AW, Vivian JP, Rossjohn J J Biol Chem. 2023 Jun 15:104930. doi: 10.1016/j.jbc.2023.104930. PMID:37330172[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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