+Open data
-Basic information
Entry | Database: PDB / ID: 7fje | ||||||
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Title | Cryo-EM structure of a membrane protein(LL) | ||||||
Components |
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Keywords | IMMUNE SYSTEM / membrane / immune | ||||||
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 / T cell activation involved in immune response / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / 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 / T cell activation involved in immune response / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / negative thymic T cell selection / Fc-gamma receptor signaling pathway / positive regulation of CD4-positive, alpha-beta T cell proliferation / alpha-beta T cell receptor complex / positive thymic T cell selection / positive regulation of protein localization to cell surface / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion / T cell receptor complex / smoothened signaling pathway / establishment or maintenance of cell polarity / positive regulation of interleukin-4 production / dendrite development / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / 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 calcium-mediated signaling / negative regulation of smoothened signaling pathway / positive regulation of T cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / T cell costimulation / T cell activation / positive regulation of interleukin-2 production / cerebellum development / FCGR3A-mediated IL10 synthesis / protein tyrosine kinase binding / calcium-mediated signaling / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / response to bacterium / clathrin-coated endocytic vesicle membrane / Regulation of actin dynamics for phagocytic cup formation / SH3 domain binding / transmembrane signaling receptor activity / peptide antigen binding / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of type II interferon production / cell-cell junction / protein transport / signaling receptor complex adaptor activity / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / protein complex oligomerization / 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 / cell surface / endoplasmic reticulum / protein homodimerization activity / identical protein binding / membrane / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | ||||||
Authors | Chen, Y. / Zhu, Y. / Gao, W. / Zhang, A. / Guo, C. / Huang, Z. | ||||||
Funding support | China, 1items
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Citation | Journal: Mol Cell / Year: 2022 Title: Cholesterol inhibits TCR signaling by directly restricting TCR-CD3 core tunnel motility. Authors: Yan Chen / Yuwei Zhu / Xiang Li / Wenbo Gao / Ziqi Zhen / De Dong / Buliao Huang / Zhuo Ma / Anqi Zhang / Xiaocui Song / Yan Ma / Changyou Guo / Fan Zhang / Zhiwei Huang / Abstract: Cholesterol molecules specifically bind to the resting αβTCR to inhibit cytoplasmic CD3ζ ITAM phosphorylation through sequestering the TCR-CD3 complex in an inactive conformation. The mechanisms ...Cholesterol molecules specifically bind to the resting αβTCR to inhibit cytoplasmic CD3ζ ITAM phosphorylation through sequestering the TCR-CD3 complex in an inactive conformation. The mechanisms of cholesterol-mediated inhibition of TCR-CD3 and its activation remain unclear. Here, we present cryoelectron microscopy structures of cholesterol- and cholesterol sulfate (CS)-inhibited TCR-CD3 complexes and an auto-active TCR-CD3 variant. The structures reveal that cholesterol molecules act like a latch to lock CD3ζ into an inactive conformation in the membrane. Mutations impairing binding of cholesterol molecules to the tunnel result in the movement of the proximal C terminus of the CD3ζ transmembrane helix, thereby activating the TCR-CD3 complex in human cells. Together, our data reveal the structural basis of TCR inhibition by cholesterol, illustrate how the cholesterol-binding tunnel is allosterically coupled to TCR triggering, and lay a foundation for the development of immunotherapies through directly targeting the TCR-CD3 complex. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7fje.cif.gz | 201.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7fje.ent.gz | 158.8 KB | Display | PDB format |
PDBx/mmJSON format | 7fje.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7fje_validation.pdf.gz | 884.9 KB | Display | wwPDB validaton report |
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Full document | 7fje_full_validation.pdf.gz | 884.8 KB | Display | |
Data in XML | 7fje_validation.xml.gz | 32.3 KB | Display | |
Data in CIF | 7fje_validation.cif.gz | 49.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fj/7fje ftp://data.pdbj.org/pub/pdb/validation_reports/fj/7fje | HTTPS FTP |
-Related structure data
Related structure data | 31619MC 7fjdC 7fjfC M: map data used to model this data C: citing same article (ref.) |
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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
-T-cell surface glycoprotein CD3 ... , 4 types, 6 molecules abdefg
#1: Protein | Mass: 18810.520 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD247, CD3Z, T3Z, TCRZ / Production host: Homo sapiens (human) / References: UniProt: P20963 #2: 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 / Production host: Homo sapiens (human) / References: UniProt: P04234 #3: 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 / Production host: Homo sapiens (human) / References: UniProt: P07766 #4: Protein | | Mass: 20493.457 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CD3G, T3G / Production host: Homo sapiens (human) / References: UniProt: P09693 |
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-T cell receptor ... , 2 types, 2 molecules mn
#5: Protein | Mass: 30763.717 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TRAV12-3, Tcr-alpha, TRAC, TCRA / Production host: Homo sapiens (human) References: UniProt: A0A0B4J271, UniProt: A0N4Z6, UniProt: P01848 |
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#6: Protein | Mass: 34529.895 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TRBV6-5, TRB, TRBC2 / Production host: Homo sapiens (human) References: UniProt: A0A0K0K1A5, UniProt: P0DSE2, UniProt: A0A0G2JMB4 |
-Non-polymers , 1 types, 1 molecules
#7: Chemical | ChemComp-CLR / |
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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: immune system / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: NITROGEN |
-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 |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1126031 / Symmetry type: POINT |