+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-44417 | |||||||||||||||||||||
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Title | TCR GDN detergent micelle | |||||||||||||||||||||
Map data | GDN_Local_unsharpened | |||||||||||||||||||||
Sample |
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Keywords | T-cell receptor / TCR / 1G4 / nanodisc / CD3 / IMMUNE SYSTEM | |||||||||||||||||||||
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 | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||
Authors | Notti RQ / Walz T | |||||||||||||||||||||
Funding support | United States, 6 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_44417.map.gz | 51.6 MB | EMDB map data format | |
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Header (meta data) | emd-44417-v30.xml emd-44417.xml | 30.5 KB 30.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_44417_fsc.xml | 9.9 KB | Display | FSC data file |
Images | emd_44417.png | 34.1 KB | ||
Filedesc metadata | emd-44417.cif.gz | 7.2 KB | ||
Others | emd_44417_additional_1.map.gz emd_44417_additional_2.map.gz emd_44417_additional_3.map.gz emd_44417_additional_4.map.gz emd_44417_half_map_1.map.gz emd_44417_half_map_2.map.gz | 89.1 MB 97.2 MB 97.2 MB 51.4 MB 95.5 MB 95.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-44417 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44417 | HTTPS FTP |
-Validation report
Summary document | emd_44417_validation.pdf.gz | 812.4 KB | Display | EMDB validaton report |
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Full document | emd_44417_full_validation.pdf.gz | 811.9 KB | Display | |
Data in XML | emd_44417_validation.xml.gz | 18.3 KB | Display | |
Data in CIF | emd_44417_validation.cif.gz | 23.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44417 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44417 | HTTPS FTP |
-Related structure data
Related structure data | 9bbcMC 8tw4C 8tw6C 9c3eC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_44417.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | GDN_Local_unsharpened | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: GDN Local DeepEMhancer
File | emd_44417_additional_1.map | ||||||||||||
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Annotation | GDN_Local_DeepEMhancer | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: GDN Local Bfactorsharp
File | emd_44417_additional_2.map | ||||||||||||
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Annotation | GDN_Local_Bfactorsharp | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: GDN nonuniform Bfactorsharp
File | emd_44417_additional_3.map | ||||||||||||
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Annotation | GDN_nonuniform_Bfactorsharp | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: GDN nonuniform unsharpened
File | emd_44417_additional_4.map | ||||||||||||
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Annotation | GDN_nonuniform_unsharpened | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: GDN Local HalfA
File | emd_44417_half_map_1.map | ||||||||||||
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Annotation | GDN_Local_HalfA | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: GDN Local HalfB
File | emd_44417_half_map_2.map | ||||||||||||
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Annotation | GDN_Local_HalfB | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : TCR in GDN micelles
Entire | Name: TCR in GDN micelles |
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Components |
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-Supramolecule #1: TCR in GDN micelles
Supramolecule | Name: TCR in GDN micelles / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #3-#4, #6 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: TCRa
Macromolecule | Name: TCRa / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 30.301111 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: METLLGLLIL WLQLQWVSSK QEVTQIPAAL SVPEGENLVL NCSFTDSAIY NLQWFRQDPG KGLTSLLLIQ SSQREQTSGR LNASLDKSS GRSTLYIAAS QPGDSATYLC AVRPLYGGSY IPTFGRGTSL IVHPYIQNPD PAVYQLRDSK SSDKSVCLFT D FDSQTNVS ...String: METLLGLLIL WLQLQWVSSK QEVTQIPAAL SVPEGENLVL NCSFTDSAIY NLQWFRQDPG KGLTSLLLIQ SSQREQTSGR LNASLDKSS GRSTLYIAAS QPGDSATYLC AVRPLYGGSY IPTFGRGTSL IVHPYIQNPD PAVYQLRDSK SSDKSVCLFT D FDSQTNVS QSKDSDVYIT DKTVLDMRSM DFKSNSAVAW SNKSDFACAN AFNNSIIPED TFFPSPESSC DVKLVEKSFE TD TNLNFQN LSVIGFRILL LKVAGFNLLM TLRLWS |
-Macromolecule #2: TCRb
Macromolecule | Name: TCRb / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 33.687016 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSIGLLCCAA LSLLWAGPVN AGVTQTPKFQ VLKTGQSMTL QCAQDMNHEY MSWYRQDPGM GLRLIHYSVG AGITDQGEVP NGYNVSRST TEDFPLRLLS AAPSQTSVYF CASSYVGNTG ELFFGEGSRL TVLEDLKNVF PPEVAVFEPS EAEISHTQKA T LVCLATGF ...String: MSIGLLCCAA LSLLWAGPVN AGVTQTPKFQ VLKTGQSMTL QCAQDMNHEY MSWYRQDPGM GLRLIHYSVG AGITDQGEVP NGYNVSRST TEDFPLRLLS AAPSQTSVYF CASSYVGNTG ELFFGEGSRL TVLEDLKNVF PPEVAVFEPS EAEISHTQKA T LVCLATGF YPDHVELSWW VNGKEVHSGV STDPQPLKEQ PALNDSRYCL SSRLRVSATF WQNPRNHFRC QVQFYGLSEN DE WTQDRAK PVTQIVSAEA WGRADCGFTS ESYQQGVLSA TILYEILLGK ATLYAVLVSA LVLMAMVK |
-Macromolecule #3: T-cell surface glycoprotein CD3 delta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 delta chain / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 18.949537 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEHSTFLSGL VLATLLSQVS PFKIPIEELE DRVFVNCNTS ITWVEGTVGT LLSDITRLDL GKRILDPRGI YRCNGTDIYK DKESTVQVH YRMCQSCVEL DPATVAGIIV TDVIATLLLA LGVFCFAGHE TGRLSGAADT QALLRNDQVY QPLRDRDDAQ Y SHLGGNWA RNK UniProtKB: T-cell surface glycoprotein CD3 delta chain |
-Macromolecule #4: T-cell surface glycoprotein CD3 epsilon chain
Macromolecule | Name: T-cell surface glycoprotein CD3 epsilon chain / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 23.174227 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP QYPGSEILWQ HNDKNIGGDE DDKNIGSDED HLSLKEFSE LEQSGYYVCY PRGSKPEDAN FYLYLRARVC ENCMEMDVMS VATIVIVDIC ITGGLLLLVY YWSKNRKAKA K PVTRGAGA ...String: MQSGTHWRVL GLCLLSVGVW GQDGNEEMGG ITQTPYKVSI SGTTVILTCP QYPGSEILWQ HNDKNIGGDE DDKNIGSDED HLSLKEFSE LEQSGYYVCY PRGSKPEDAN FYLYLRARVC ENCMEMDVMS VATIVIVDIC ITGGLLLLVY YWSKNRKAKA K PVTRGAGA GGRQRGQNKE RPPPVPNPDY EPIRKGQRDL YSGLNQRRI UniProtKB: T-cell surface glycoprotein CD3 epsilon chain |
-Macromolecule #5: T-cell surface glycoprotein CD3 gamma chain
Macromolecule | Name: T-cell surface glycoprotein CD3 gamma chain / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 15.220763 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEQGKGLAVL ILAIILLQGT LAQSIKGNHL VKVYDYQEDG SVLLTCDAEA KNITWFKDGK MIGFLTEDKK KWNLGSNAKD PRGMYQCKG SQNKSKPLQV YYRMCQNCIE LNAATISGFL FAEIVSIFVL AVGVYFIA UniProtKB: T-cell surface glycoprotein CD3 gamma chain |
-Macromolecule #6: T-cell surface glycoprotein CD3 zeta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 zeta chain / type: protein_or_peptide / ID: 6 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 18.723439 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKR RGRDPEMGGK PQRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT KDTYDALHMQ A LPPR UniProtKB: T-cell surface glycoprotein CD3 zeta chain |
-Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 9 / Number of copies: 5 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #10: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 10 / Number of copies: 2 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: GRAPHENE OXIDE / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 51.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.0 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 64000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |