+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31619 | |||||||||
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Title | Cryo-EM structure of a membrane protein(LL) | |||||||||
Map data | ||||||||||
Sample |
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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 | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Chen Y / Zhu Y / Gao W / Zhang A / Guo C / Huang Z | |||||||||
Funding support | China, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_31619.map.gz | 59.7 MB | EMDB map data format | |
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Header (meta data) | emd-31619-v30.xml emd-31619.xml | 15.9 KB 15.9 KB | Display Display | EMDB header |
Images | emd_31619.png | 82.2 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31619 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31619 | HTTPS FTP |
-Validation report
Summary document | emd_31619_validation.pdf.gz | 448.7 KB | Display | EMDB validaton report |
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Full document | emd_31619_full_validation.pdf.gz | 448.3 KB | Display | |
Data in XML | emd_31619_validation.xml.gz | 6.1 KB | Display | |
Data in CIF | emd_31619_validation.cif.gz | 6.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31619 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31619 | HTTPS FTP |
-Related structure data
Related structure data | 7fjeMC 7fjdC 7fjfC 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_31619.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : immune system
Entire | Name: immune system |
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Components |
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-Supramolecule #1: immune system
Supramolecule | Name: immune system / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Macromolecule #1: T-cell surface glycoprotein CD3 zeta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 zeta chain / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 18.81052 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 LPPRS |
-Macromolecule #2: T-cell surface glycoprotein CD3 delta chain
Macromolecule | Name: T-cell surface glycoprotein CD3 delta chain / 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: 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 |
-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: 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 |
-Macromolecule #4: T-cell surface glycoprotein CD3 gamma chain
Macromolecule | Name: T-cell surface glycoprotein CD3 gamma chain / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 20.493457 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 LRRN |
-Macromolecule #5: T cell receptor alpha variable 12-3,Possible J 11 gene segment,T ...
Macromolecule | Name: T cell receptor alpha variable 12-3,Possible J 11 gene segment,T cell receptor alpha chain constant 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: 30.763717 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MKSLRVLLVI LWLQLSWVWS QQKEVEQDPG PLSVPEGAIV SLNCTYSNSA FQYFMWYRQY SRKGPELLMY TYSSGNKEDG RFTAQVDKS SKYISLFIRD SQPSDSATYL CAMSKGYSTL TFGKGTMLLV SPDIQNPDPA VYQLRDSKSS DKSVCLFTDF D SQTNVSQS ...String: MKSLRVLLVI LWLQLSWVWS QQKEVEQDPG PLSVPEGAIV SLNCTYSNSA FQYFMWYRQY SRKGPELLMY TYSSGNKEDG RFTAQVDKS SKYISLFIRD SQPSDSATYL CAMSKGYSTL TFGKGTMLLV SPDIQNPDPA VYQLRDSKSS DKSVCLFTDF D SQTNVSQS KDSDVYITDK TVLDMRSMDF KSNSAVAWSN KSDFACANAF NNSIIPEDTF FPSPESSCDV KLVEKSFETD TN LNFQNLS VIGFRILLLK VAGFNLLMTL RLWSS |
-Macromolecule #6: T cell receptor beta variable 6-5,M1-specific T cell receptor bet...
Macromolecule | Name: T cell receptor beta variable 6-5,M1-specific T cell receptor beta chain,T cell receptor beta constant 2 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: 34.529895 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MSISLLCCAA LSLLWAGPVN AGVTQTPKFQ VLKTGQSMTL QCAQDMNHEY MSWYRQDPGM GLRLIHYSVG AGITDQGEVP NGYNVSRST TEDFPLRLLS AAPSQTSVYF CASRRRQGAS GEQYFGPGTR LTVTEDLKNV FPPEVAVFEP SEAEISHTQK A TLVCLATG ...String: MSISLLCCAA LSLLWAGPVN AGVTQTPKFQ VLKTGQSMTL QCAQDMNHEY MSWYRQDPGM GLRLIHYSVG AGITDQGEVP NGYNVSRST TEDFPLRLLS AAPSQTSVYF CASRRRQGAS GEQYFGPGTR LTVTEDLKNV FPPEVAVFEP SEAEISHTQK A TLVCLATG FYPDHVELSW WVNGKEVHSG VSTDPQPLKE QPALNDSRYC LSSRLRVSAT FWQNPRNHFR CQVQFYGLSE ND EWTQDRA KPVTQIVSAE AWGRADCGFT SESYQQGVLS ATIAYEIALG KATLYAVLVS ALVLMAMVKR KDSRG |
-Macromolecule #7: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 1 / 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
Buffer | pH: 8 |
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Vitrification | Cryogen name: NITROGEN |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1126031 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |