9bbc: Difference between revisions
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The | ==TCR GDN detergent micelle== | ||
<StructureSection load='9bbc' size='340' side='right'caption='[[9bbc]], [[Resolution|resolution]] 3.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9bbc]] is a 8 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=9BBC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BBC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=9bbc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9bbc OCA], [https://pdbe.org/9bbc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9bbc RCSB], [https://www.ebi.ac.uk/pdbsum/9bbc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9bbc ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/CD3D_HUMAN CD3D_HUMAN] Defects in CD3D are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:[https://omim.org/entry/608971 608971]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.<ref>PMID:14602880</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CD3D_HUMAN CD3D_HUMAN] The CD3 complex mediates signal transduction. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( 1-4 ). Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte antigen (HLA)-bound human TCR-CD3 complex in nanodiscs that provide a native-like lipid environment. Distinct from the "open and extended" conformation seen in detergent( 5-8 ), the unliganded TCR-CD3 in nanodiscs adopts two related "closed and compacted" conformations that represent its physiologic resting state in vivo . By contrast, the HLA-bound complex adopts the open and extended conformation, and conformation-locking disulfide mutants show that ectodomain opening is necessary for maximal ligand-dependent T-cell activation. Together, these results reveal allosteric conformational change during TCR activation and highlight the importance of native-like lipid environments for membrane protein structure determination. | |||
The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.,Notti RQ, Yi F, Heissel S, Bush MW, Molvi Z, Das P, Molina H, Klebanoff CA, Walz T bioRxiv [Preprint]. 2024 Sep 20:2023.08.22.554360. doi: , 10.1101/2023.08.22.554360. PMID:37662363<ref>PMID:37662363</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9bbc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Notti RQ]] | |||
[[Category: Walz T]] | |||
Latest revision as of 07:03, 5 October 2024
TCR GDN detergent micelleTCR GDN detergent micelle
Structural highlights
DiseaseCD3D_HUMAN Defects in CD3D are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:608971. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.[1] FunctionCD3D_HUMAN The CD3 complex mediates signal transduction. Publication Abstract from PubMedThe T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( 1-4 ). Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte antigen (HLA)-bound human TCR-CD3 complex in nanodiscs that provide a native-like lipid environment. Distinct from the "open and extended" conformation seen in detergent( 5-8 ), the unliganded TCR-CD3 in nanodiscs adopts two related "closed and compacted" conformations that represent its physiologic resting state in vivo . By contrast, the HLA-bound complex adopts the open and extended conformation, and conformation-locking disulfide mutants show that ectodomain opening is necessary for maximal ligand-dependent T-cell activation. Together, these results reveal allosteric conformational change during TCR activation and highlight the importance of native-like lipid environments for membrane protein structure determination. The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex.,Notti RQ, Yi F, Heissel S, Bush MW, Molvi Z, Das P, Molina H, Klebanoff CA, Walz T bioRxiv [Preprint]. 2024 Sep 20:2023.08.22.554360. doi: , 10.1101/2023.08.22.554360. PMID:37662363[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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