+Open data
-Basic information
Entry | Database: PDB / ID: 9bbc | |||||||||||||||||||||
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Title | TCR GDN detergent micelle | |||||||||||||||||||||
Components |
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Keywords | IMMUNE SYSTEM / T-cell receptor / TCR / 1G4 / nanodisc / CD3 | |||||||||||||||||||||
Function / homology | Function and homology information regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / T cell anergy / positive regulation of T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / Fc-gamma receptor signaling pathway / negative thymic T cell selection ...regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / T cell anergy / positive regulation of T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / Fc-gamma receptor signaling pathway / negative thymic T cell selection / positive regulation of CD4-positive, alpha-beta T cell proliferation / alpha-beta T cell receptor complex / positive regulation of protein localization to cell surface / positive thymic T cell selection / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion / T cell receptor complex / establishment or maintenance of cell polarity / smoothened signaling pathway / positive regulation of interleukin-4 production / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / dendrite development / alpha-beta T cell activation / Generation of second messenger molecules / immunological synapse / FCGR activation / PD-1 signaling / Role of phospholipids in phagocytosis / T cell receptor binding / positive regulation of T cell proliferation / negative regulation of smoothened signaling pathway / cell surface receptor protein tyrosine kinase signaling pathway / T cell costimulation / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / T cell activation / FCGR3A-mediated IL10 synthesis / cerebellum development / protein tyrosine kinase binding / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / protein complex oligomerization / Regulation of actin dynamics for phagocytic cup formation / SH3 domain binding / positive regulation of type II interferon production / positive regulation of peptidyl-tyrosine phosphorylation / transmembrane signaling receptor activity / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / cell-cell junction / protein transport / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / Downstream TCR signaling / Clathrin-mediated endocytosis / T cell receptor signaling pathway / cell body / protein-containing complex assembly / regulation of apoptotic process / adaptive immune response / dendritic spine / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / protein heterodimerization activity / external side of plasma membrane / negative regulation of gene expression / positive regulation of gene expression / protein kinase binding / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||
Authors | Notti, R.Q. / Walz, T. | |||||||||||||||||||||
Funding support | United States, 6items
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Citation | Journal: bioRxiv / Year: 2024 Title: The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex. Authors: Ryan Q Notti / Fei Yi / Søren Heissel / Martin W Bush / Zaki Molvi / Pujita Das / Henrik Molina / Christopher A Klebanoff / Thomas Walz Abstract: The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( ). Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte ...The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( ). 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( ), the unliganded TCR-CD3 in nanodiscs adopts two related "closed and compacted" conformations that represent its physiologic resting state . 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. | |||||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9bbc.cif.gz | 218.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9bbc.ent.gz | 168.6 KB | Display | PDB format |
PDBx/mmJSON format | 9bbc.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9bbc_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 9bbc_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 9bbc_validation.xml.gz | 49.3 KB | Display | |
Data in CIF | 9bbc_validation.cif.gz | 71.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bb/9bbc ftp://data.pdbj.org/pub/pdb/validation_reports/bb/9bbc | HTTPS FTP |
-Related structure data
Related structure data | 44417MC 8tw4C 8tw6C 9c3eC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 30301.111 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
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#2: Protein | Mass: 33687.016 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293F / Production host: Homo sapiens (human) |
-T-cell surface glycoprotein CD3 ... , 4 types, 6 molecules DEFGXY
#3: Protein | Mass: 18949.537 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3D, T3D / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P04234 | ||||
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#4: Protein | Mass: 23174.227 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3E, T3E / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P07766 #5: Protein | | Mass: 15220.763 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3G, T3G / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P09693 #6: Protein | Mass: 18723.439 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD247, CD3Z, T3Z, TCRZ / Cell line (production host): HEK293F / Production host: Homo sapiens (human) / References: UniProt: P20963 |
-Sugars , 3 types, 10 molecules
#7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | Source method: isolated from a genetically manipulated source #9: Sugar | ChemComp-NAG / |
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-Non-polymers , 1 types, 2 molecules
#10: Chemical |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: TCR in GDN micelles / Type: COMPLEX / Entity ID: #3-#4, #6 / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Strain: HEK293F | ||||||||||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 64000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 800 nm / Cs: 0 mm |
Image recording | Electron dose: 51 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
EM software | Name: PHENIX / Version: 1.21_5207: / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 252000 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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