+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41660 | |||||||||||||||||||||
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Title | TCR in nanodisc ND-II | |||||||||||||||||||||
Map data | unsharpened map | |||||||||||||||||||||
Sample |
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Keywords | T-cell receptor / TCR / 1G4 / nanodisc / CD3 / IMMUNE SYSTEM | |||||||||||||||||||||
Function / homology | Function and homology information detection of tumor cell / 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 / gamma-delta T cell activation / CD4-positive, alpha-beta T cell proliferation / negative thymic T cell selection ...detection of tumor cell / 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 / gamma-delta T cell activation / CD4-positive, alpha-beta T cell proliferation / 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 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 mediated cytotoxicity directed against tumor cell target / T cell receptor complex / smoothened signaling pathway / establishment or maintenance of cell polarity / positive regulation of interleukin-4 production / protein complex oligomerization / 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 / negative regulation of smoothened signaling pathway / positive regulation of T cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / T cell costimulation / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / FCGR3A-mediated IL10 synthesis / cerebellum development / bioluminescence / protein tyrosine kinase binding / T cell activation / apoptotic signaling pathway / generation of precursor metabolites and energy / FCGR3A-mediated phagocytosis / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / Regulation of actin dynamics for phagocytic cup formation / SH3 domain binding / positive regulation of type II interferon production / positive regulation of peptidyl-tyrosine phosphorylation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / transmembrane signaling receptor activity / cell-cell junction / protein transport / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / Clathrin-mediated endocytosis / signaling receptor activity / 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 / protein heterodimerization activity / G protein-coupled receptor signaling pathway / 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) / human respiratory syncytial virus / Escherichia coli str. K-12 substr. MG1655 (bacteria) | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 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_41660.map.gz | 51.1 MB | EMDB map data format | |
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Header (meta data) | emd-41660-v30.xml emd-41660.xml | 27.5 KB 27.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41660_fsc.xml | 9.9 KB | Display | FSC data file |
Images | emd_41660.png | 43.7 KB | ||
Filedesc metadata | emd-41660.cif.gz | 7.7 KB | ||
Others | emd_41660_additional_1.map.gz emd_41660_additional_2.map.gz emd_41660_half_map_1.map.gz emd_41660_half_map_2.map.gz | 50.8 MB 111 MB 95.7 MB 115.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41660 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41660 | HTTPS FTP |
-Validation report
Summary document | emd_41660_validation.pdf.gz | 412.4 KB | Display | EMDB validaton report |
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Full document | emd_41660_full_validation.pdf.gz | 412 KB | Display | |
Data in XML | emd_41660_validation.xml.gz | 6.5 KB | Display | |
Data in CIF | emd_41660_validation.cif.gz | 7.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41660 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41660 | HTTPS FTP |
-Related structure data
Related structure data | 8tw6MC 8tw4C 9bbcC 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_41660.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | unsharpened map | ||||||||||||||||||||||||||||||||||||
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: B-factor sharpened
File | emd_41660_additional_1.map | ||||||||||||
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Annotation | B-factor sharpened | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: unsharpened map
File | emd_41660_additional_2.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: unsharpened map
File | emd_41660_half_map_1.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: unsharpened map
File | emd_41660_half_map_2.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : TCR hetero-octamer in lipid nanodisc
Entire | Name: TCR hetero-octamer in lipid nanodisc |
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Components |
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-Supramolecule #1: TCR hetero-octamer in lipid nanodisc
Supramolecule | Name: TCR hetero-octamer in lipid nanodisc / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: T-cell surface glycoprotein CD3 zeta chain, GFP fusion protein,GFP
Macromolecule | Name: T-cell surface glycoprotein CD3 zeta chain, GFP fusion protein,GFP type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: human respiratory syncytial virus |
Molecular weight | Theoretical: 46.650879 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 LPPRASLE ...String: MKWKALFTAA ILQAQLPITE AQSFGLLDPK LCYLLDGILF IYGVILTALF LRVKFSRSAD APAYQQGQNQ LYNELNLGRR EEYDVLDKR RGRDPEMGGK PQRRKNPQEG LYNELQKDKM AEAYSEIGMK GERRRGKGHD GLYQGLSTAT KDTYDALHMQ A LPPRASLE VLFQGPVSKG EELFTGVVPI LVELDGDVNG HKFSVSGEGE GDATYGKLTL KFICTTGKLP VPWPTLVTTL TY GVQCFSR YPDHMKQHDF FKSAMPEGYV QERTIFFKDD GNYKTRAEVK FEGDTLVNRI ELKGIDFKED GNILGHKLEY NYN SHNVYI MADKQKNGIK VNFKIRHNIE DGSVQLADHY QQNTPIGDGP VLLPDNHYLS TQSKLSKDPN EKRDHMVLLE FVTA AGITL GMDELYK UniProtKB: T-cell surface glycoprotein CD3 zeta chain, GFP |
-Macromolecule #2: TCR alpha
Macromolecule | Name: TCR alpha / 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: 30.388189 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 TLRLWSS |
-Macromolecule #3: T cell receptor beta variable 6-5,T cell receptor beta chain MC.7...
Macromolecule | Name: T cell receptor beta variable 6-5,T cell receptor beta chain MC.7.G5,MCHERRY type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Escherichia coli str. K-12 substr. MG1655 (bacteria) |
Molecular weight | Theoretical: 62.042883 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 LVLMAMVKRK DSRGASLEVL FQG PVSKGE EDNMAIIKEF MRFKVHMEGS VNGHEFEIEG EGEGRPYEGT QTAKLKVTKG GPLPFAWDIL SPQFMYGSKA YVKH PADIP DYLKLSFPEG FKWERVMNFE DGGVVTVTQD SSLQDGEFIY KVKLRGTNFP SDGPVMQKKT MGWEASSERM YPEDG ALKG EIKQRLKLKD GGHYDAEVKT TYKAKKPVQL PGAYNVNIKL DITSHNEDYT IVEQYERAEG RHSTGGMDEL YK UniProtKB: T cell receptor beta variable 6-5, T cell receptor beta chain MC.7.G5, MCHERRY |
-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 delta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 delta 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: 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 #6: T-cell surface glycoprotein CD3 gamma chain
Macromolecule | Name: T-cell surface glycoprotein CD3 gamma chain / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 21.598633 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MEQGKGLAVL ILAIILLQGT LAQSIKGNHL VKVYDYQEDG SVLLTCDAEA KNITWFKDGK MIGFLTEDKK KWNLGSNAKD PRGMYQCKG SQNKSKPLQV YYRMCQNCIE LNAATISGFL FAEIVSIFVL AVGVYFIAGQ DGVRQSRASD KQTLLPNDQL Y QPLKDRED DQYSHLQGNQ LRRNHHHHHH HH UniProtKB: T-cell surface glycoprotein CD3 gamma chain |
-Macromolecule #8: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 8 / Number of copies: 2 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-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: 1 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.330 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. | |||||||||
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: 57.0 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: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 64000 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |