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Title | TCR in nanodisc ND-I | |||||||||||||||||||||
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![]() | T-cell receptor / TCR / 1G4 / nanodisc / CD3 / IMMUNE SYSTEM | |||||||||||||||||||||
Function / homology | ![]() detection of tumor cell / regulation of lymphocyte apoptotic process / NNS virus cap methyltransferase / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / GDP polyribonucleotidyltransferase / T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / positive regulation of T cell anergy / gamma-delta T cell activation ...detection of tumor cell / regulation of lymphocyte apoptotic process / NNS virus cap methyltransferase / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / GDP polyribonucleotidyltransferase / T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / positive regulation of T cell anergy / gamma-delta T cell activation / Fc-gamma receptor signaling pathway / CD4-positive, alpha-beta T cell proliferation / 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 / T cell mediated cytotoxicity directed against tumor cell target / positive regulation of cell-matrix adhesion / T cell receptor complex / smoothened signaling pathway / establishment or maintenance of cell polarity / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / positive regulation of interleukin-4 production / dendrite development / protein complex oligomerization / alpha-beta T cell activation / Generation of second messenger molecules / FCGR activation / immunological synapse / Co-inhibition by PD-1 / Role of phospholipids in phagocytosis / T cell receptor binding / positive regulation of T cell proliferation / T cell costimulation / positive regulation of interleukin-2 production / cerebellum development / FCGR3A-mediated IL10 synthesis / positive regulation of calcium-mediated signaling / T cell activation / bioluminescence / cell surface receptor protein tyrosine kinase signaling pathway / protein tyrosine kinase binding / generation of precursor metabolites and energy / negative regulation of smoothened signaling pathway / FCGR3A-mediated phagocytosis / apoptotic signaling pathway / clathrin-coated endocytic vesicle membrane / calcium-mediated signaling / SH3 domain binding / Regulation of actin dynamics for phagocytic cup formation / virion component / positive regulation of type II interferon production / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / transmembrane signaling receptor activity / protein transport / cell-cell junction / Downstream TCR signaling / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / T cell receptor signaling pathway / signaling receptor activity / Clathrin-mediated endocytosis / cell body / protein-containing complex assembly / regulation of apoptotic process / dendritic spine / adaptive immune response / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / cell surface receptor signaling pathway / hydrolase activity / G protein-coupled receptor signaling pathway / protein heterodimerization activity / external side of plasma membrane / negative regulation of gene expression / RNA-directed RNA polymerase / RNA-directed RNA polymerase activity / positive regulation of gene expression / protein kinase binding / endoplasmic reticulum / Golgi apparatus / protein homodimerization activity / ATP binding / metal ion binding / identical protein binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||||||||||||||
![]() | Notti RQ / Walz T | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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
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Downloads & links
-EMDB archive
Map data | ![]() | 51 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 31.5 KB 31.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.9 KB | Display | ![]() |
Images | ![]() | 34.6 KB | ||
Filedesc metadata | ![]() | 7.9 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() ![]() | 91.5 MB 97.1 MB 97.1 MB 50.7 MB 95.6 MB 95.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8tw4MC ![]() 8tw6C ![]() 9bbcC ![]() 9c3eC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: unsharpened
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-Additional map: #2
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-Additional map: #1
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-Half map: unsharpened
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Sample components
-Entire : Hetero-octameric TCR complex embedded in a lipid nanodisc
Entire | Name: Hetero-octameric TCR complex embedded in a lipid nanodisc |
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Components |
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-Supramolecule #1: Hetero-octameric TCR complex embedded in a lipid nanodisc
Supramolecule | Name: Hetero-octameric TCR complex embedded in a lipid nanodisc type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: TCR alpha
Macromolecule | Name: TCR alpha / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 30.388189 KDa |
Recombinant expression | Organism: ![]() |
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 #2: T cell receptor beta variable 6-5, T cell receptor beta chain MC....
Macromolecule | Name: T cell receptor beta variable 6-5, T cell receptor beta chain MC.7.G5, MCHERRY fusion protein type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 62.042883 KDa |
Recombinant expression | Organism: ![]() |
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 #3: T-cell surface glycoprotein CD3 epsilon chain
Macromolecule | Name: T-cell surface glycoprotein CD3 epsilon chain / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.174227 KDa |
Recombinant expression | Organism: ![]() |
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 #4: T-cell surface glycoprotein CD3 delta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 delta chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 18.949537 KDa |
Recombinant expression | Organism: ![]() |
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 #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: ![]() |
Molecular weight | Theoretical: 21.598633 KDa |
Recombinant expression | Organism: ![]() |
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 #6: T-cell surface glycoprotein CD3 zeta chain,RNA-directed RNA polym...
Macromolecule | Name: T-cell surface glycoprotein CD3 zeta chain,RNA-directed RNA polymerase L type: protein_or_peptide / ID: 6 / Number of copies: 2 / Enantiomer: LEVO / EC number: NNS virus cap methyltransferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 46.650879 KDa |
Recombinant expression | Organism: ![]() |
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, RNA-directed RNA polymerase L |
-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: 3 / 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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![]() | single particle reconstruction |
Aggregation state | particle |
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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 / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | TFS 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: ![]() |
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 |