+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-6668 | ||||||||||||||||||
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Title | Cryo-EM structure of mTORC1 | ||||||||||||||||||
Map data | |||||||||||||||||||
Sample |
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Function / homology | Function and homology information RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / TORC2 complex ...RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / regulation of locomotor rhythm / positive regulation of wound healing, spreading of epidermal cells / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / TORC2 complex / regulation of membrane permeability / heart valve morphogenesis / negative regulation of lysosome organization / RNA polymerase III type 3 promoter sequence-specific DNA binding / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / TORC1 complex / calcineurin-NFAT signaling cascade / nucleus localization / cellular response to methionine / voluntary musculoskeletal movement / regulation of osteoclast differentiation / positive regulation of odontoblast differentiation / TORC1 signaling / positive regulation of keratinocyte migration / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / regulation of autophagosome assembly / Energy dependent regulation of mTOR by LKB1-AMPK / energy reserve metabolic process / negative regulation of cell size / ruffle organization / protein serine/threonine kinase inhibitor activity / positive regulation of osteoclast differentiation / cellular response to osmotic stress / negative regulation of protein localization to nucleus / enzyme-substrate adaptor activity / anoikis / cardiac muscle cell development / positive regulation of transcription by RNA polymerase III / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / negative regulation of macroautophagy / regulation of cell size / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of oligodendrocyte differentiation / Macroautophagy / positive regulation of actin filament polymerization / lysosome organization / positive regulation of myotube differentiation / protein kinase activator activity / oligodendrocyte differentiation / behavioral response to pain / Constitutive Signaling by AKT1 E17K in Cancer / germ cell development / mTORC1-mediated signalling / CD28 dependent PI3K/Akt signaling / : / social behavior / HSF1-dependent transactivation / neuronal action potential / TOR signaling / positive regulation of TOR signaling / response to amino acid / endomembrane system / cellular response to nutrient levels / positive regulation of translational initiation / regulation of macroautophagy / 'de novo' pyrimidine nucleobase biosynthetic process / positive regulation of lamellipodium assembly / positive regulation of epithelial to mesenchymal transition / positive regulation of lipid biosynthetic process / heart morphogenesis / response to nutrient / cardiac muscle contraction / regulation of cellular response to heat / phagocytic vesicle / positive regulation of stress fiber assembly / cytoskeleton organization / 14-3-3 protein binding / Regulation of PTEN gene transcription / positive regulation of endothelial cell proliferation / T cell costimulation / cellular response to starvation / phosphorylation / positive regulation of glycolytic process / cellular response to amino acid starvation / protein serine/threonine kinase activator activity / response to nutrient levels / negative regulation of autophagy / cellular response to amino acid stimulus / VEGFR2 mediated vascular permeability / post-embryonic development / positive regulation of peptidyl-threonine phosphorylation / regulation of signal transduction by p53 class mediator / regulation of autophagy / positive regulation of translation / regulation of circadian rhythm / regulation of cell growth Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.4 Å | ||||||||||||||||||
Authors | Yang H / Wang J / Liu M / Chen X / Huang M / Tan D / Dong M / Wong CCL / Xu Y / Wang H | ||||||||||||||||||
Funding support | China, 5 items
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Citation | Journal: Protein Cell / Year: 2016 Title: 4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1. Authors: Huirong Yang / Jia Wang / Mengjie Liu / Xizi Chen / Min Huang / Dan Tan / Meng-Qiu Dong / Catherine C L Wong / Jiawei Wang / Yanhui Xu / Hong-Wei Wang / Abstract: Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through ...Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 Å resolution. The mTORC1 comprises a dimer of heterotrimer (mTOR-Raptor-mLST8) mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase-like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for substrate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance for substrate entry to the catalytic cavity of mTORC1. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regulatory mechanism of mTORC1 pathway. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_6668.map.gz | 10 MB | EMDB map data format | |
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Header (meta data) | emd-6668-v30.xml emd-6668.xml | 21 KB 21 KB | Display Display | EMDB header |
Images | emd_6668.png | 155.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-6668 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6668 | HTTPS FTP |
-Validation report
Summary document | emd_6668_validation.pdf.gz | 336.8 KB | Display | EMDB validaton report |
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Full document | emd_6668_full_validation.pdf.gz | 336.4 KB | Display | |
Data in XML | emd_6668_validation.xml.gz | 6.4 KB | Display | |
Data in CIF | emd_6668_validation.cif.gz | 7.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6668 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6668 | HTTPS FTP |
-Related structure data
Related structure data | 5h64MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_6668.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.30654 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : human mTOR complex 1
Entire | Name: human mTOR complex 1 |
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Components |
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-Supramolecule #1: human mTOR complex 1
Supramolecule | Name: human mTOR complex 1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Mammalia (mammals) / Recombinant plasmid: pCAG |
Molecular weight | Experimental: 1 MDa |
-Macromolecule #1: Serine/threonine-protein kinase mTOR
Macromolecule | Name: Serine/threonine-protein kinase mTOR / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: non-specific serine/threonine protein kinase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 289.257969 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES TRFYDQLNHH IFELVSSSDA NERKGGILA IASLIGVEGG NATRIGRFAN YLRNLLPSND PVVMEMASKA IGRLAMAGDT FTAEYVEFEV KRALEWLGAD R NEGRRHAA ...String: MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES TRFYDQLNHH IFELVSSSDA NERKGGILA IASLIGVEGG NATRIGRFAN YLRNLLPSND PVVMEMASKA IGRLAMAGDT FTAEYVEFEV KRALEWLGAD R NEGRRHAA VLVLRELAIS VPTFFFQQVQ PFFDNIFVAV WDPKQAIREG AVAALRACLI LTTQREPKEM QKPQWYRHTF EE AEKGFDE TLAKEKGMNR DDRIHGALLI LNELVRISSM EGERLREEME EITQQQLVHD KYCKDLMGFG TKPRHITPFT SFQ AVQPQQ SNALVGLLGY SSHQGLMGFG TSPSPAKSTL VESRCCRDLM EEKFDQVCQW VLKCRNSKNS LIQMTILNLL PRLA AFRPS AFTDTQYLQD TMNHVLSCVK KEKERTAAFQ ALGLLSVAVR SEFKVYLPRV LDIIRAALPP KDFAHKRQKA MQVDA TVFT CISMLARAMG PGIQQDIKEL LEPMLAVGLS PALTAVLYDL SRQIPQLKKD IQDGLLKMLS LVLMHKPLRH PGMPKG LAH QLASPGLTTL PEASDVGSIT LALRTLGSFE FEGHSLTQFV RHCADHFLNS EHKEIRMEAA RTCSRLLTPS IHLISGH AH VVSQTAVQVV ADVLSKLLVV GITDPDPDIR YCVLASLDER FDAHLAQAEN LQALFVALND QVFEIRELAI CTVGRLSS M NPAFVMPFLR KMLIQILTEL EHSGIGRIKE QSARMLGHLV SNAPRLIRPY MEPILKALIL KLKDPDPDPN PGVINNVLA TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLG LLGALDPYKH KVNIGMIDQS RDASAVSLSE SKSSQDSSDY STSEMLVNMG NLPLDEFYPA VSMVALMRIF R DQSLSHHH TMVVQAITFI FKSLGLKCVQ FLPQVMPTFL NVIRVCDGAI REFLFQQLGM LVSFVKSHIR PYMDEIVTLM RE FWVMNTS IQSTIILLIE QIVVALGGEF KLYLPQLIPH MLRVFMHDNS PGRIVSIKLL AAIQLFGANL DDYLHLLLPP IVK LFDAPE APLPSRKAAL ETVDRLTESL DFTDYASRII HPIVRTLDQS PELRSTAMDT LSSLVFQLGK KYQIFIPMVN KVLV RHRIN HQRYDVLICR IVKGYTLADE EEDPLIYQHR MLRSGQGDAL ASGPVETGPM KKLHVSTINL QKAWGAARRV SKDDW LEWL RRLSLELLKD SSSPSLRSCW ALAQAYNPMA RDLFNAAFVS CWSELNEDQQ DELIRSIELA LTSQDIAEVT QTLLNL AEF MEHSDKGPLP LRDDNGIVLL GERAAKCRAY AKALHYKELE FQKGPTPAIL ESLISINNKL QQPEAAAGVL EYAMKHF GE LEIQATWYEK LHEWEDALVA YDKKMDTNKD DPELMLGRMR CLEALGEWGQ LHQQCCEKWT LVNDETQAKM ARMAAAAA W GLGQWDSMEE YTCMIPRDTH DGAFYRAVLA LHQDLFSLAQ QCIDKARDLL DAELTAMAGE SYSRAYGAMV SCHMLSELE EVIQYKLVPE RREIIRQIWW ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD PSRQLDHPL PTVHPQVTYA YMKNMWKSAR KIDAFQHMQH FVQTMQQQAQ HAIATEDQQH KQELHKLMAR CFLKLGEWQL N LQGINEST IPKVLQYYSA ATEHDRSWYK AWHAWAVMNF EAVLHYKHQN QARDEKKKLR HASGANITNA TTAATTAATA TT TASTEGS NSESEAESTE NSPTPSPLQK KVTEDLSKTL LMYTVPAVQG FFRSISLSRG NNLQDTLRVL TLWFDYGHWP DVN EALVEG VKAIQIDTWL QVIPQLIARI DTPRPLVGRL IHQLLTDIGR YHPQALIYPL TVASKSTTTA RHNAANKILK NMCE HSNTL VQQAMMVSEE LIRVAILWHE MWHEGLEEAS RLYFGERNVK GMFEVLEPLH AMMERGPQTL KETSFNQAYG RDLME AQEW CRKYMKSGNV KDLTQAWDLY YHVFRRISKQ LPQLTSLELQ YVSPKLLMCR DLELAVPGTY DPNQPIIRIQ SIAPSL QVI TSKQRPRKLT LMGSNGHEFV FLLKGHEDLR QDERVMQLFG LVNTLLANDP TSLRKNLSIQ RYAVIPLSTN SGLIGWV PH CDTLHALIRD YREKKKILLN IEHRIMLRMA PDYDHLTLMQ KVEVFEHAVN NTAGDDLAKL LWLKSPSSEV WFDRRTNY T RSLAVMSMVG YILGLGDRHP SNLMLDRLSG KILHIDFGDC FEVAMTREKF PEKIPFRLTR MLTNAMEVTG LDGNYRITC HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG VELGEPAHKK TGTTVPESIH SFIGDGLVK PEALNKKAIQ IINRVRDKLT GRDFSHDDTL DVPTQVELLI KQATSHENLC QCYIGWCPFW |
-Macromolecule #2: Regulatory-associated protein of mTOR
Macromolecule | Name: Regulatory-associated protein of mTOR / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 149.200016 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MESEMLQSPL LGLGEEDEAD LTDWNLPLAF MKKRHCEKIE GSKSLAQSWR MKDRMKTVSV ALVLCLNVGV DPPDVVKTTP CARLECWID PLSMGPQKAL ETIGANLQKQ YENWQPRARY KQSLDPTVDE VKKLCTSLRR NAKEERVLFH YNGHGVPRPT V NGEVWVFN ...String: MESEMLQSPL LGLGEEDEAD LTDWNLPLAF MKKRHCEKIE GSKSLAQSWR MKDRMKTVSV ALVLCLNVGV DPPDVVKTTP CARLECWID PLSMGPQKAL ETIGANLQKQ YENWQPRARY KQSLDPTVDE VKKLCTSLRR NAKEERVLFH YNGHGVPRPT V NGEVWVFN KNYTQYIPLS IYDLQTWMGS PSIFVYDCSN AGLIVKSFKQ FALQREQELE VAAINPNHPL AQMPLPPSMK NC IQLAACE ATELLPMIPD LPADLFTSCL TTPIKIALRW FCMQKCVSLV PGVTLDLIEK IPGRLNDRRT PLGELNWIFT AIT DTIAWN VLPRDLFQKL FRQDLLVASL FRNFLLAERI MRSYNCTPVS SPRLPPTYMH AMWQAWDLAV DICLSQLPTI IEEG TAFRH SPFFAEQLTA FQVWLTMGVE NRNPPEQLPI VLQVLLSQVH RLRALDLLGR FLDLGPWAVS LALSVGIFPY VLKLL QSSA RELRPLLVFI WAKILAVDSS CQADLVKDNG HKYFLSVLAD PYMPAEHRTM TAFILAVIVN SYHTGQEACL QGNLIA ICL EQLNDPHPLL RQWVAICLGR IWQNFDSARW CGVRDSAHEK LYSLLSDPIP EVRCAAVFAL GTFVGNSAER TDHSTTI DH NVAMMLAQLV SDGSPMVRKE LVVALSHLVV QYESNFCTVA LQFIEEEKNY ALPSPATTEG GSLTPVRDSP CTPRLRSV S SYGNIRAVAT ARSLNKSLQN LSLTEESGGA VAFSPGNLST SSSASSTLGS PENEEHILSF ETIDKMRRAS SYSSLNSLI GVSFNSVYTQ IWRVLLHLAA DPYPEVSDVA MKVLNSIAYK ATVNARPQRV LDTSSLTQSA PASPTNKGVH IHQAGGSPPA SSTSSSSLT NDVAKQPVSR DLPSGRPGTT GPAGAQYTPH SHQFPRTRKM FDKGPEQTAD DADDAAGHKS FISATVQTGF C DWSARYFA QPVMKIPEEH DLESQIRKER EWRFLRNSRV RRQAQQVIQK GITRLDDQIF LNRNPGVPSV VKFHPFTPCI AV ADKDSIC FWDWEKGEKL DYFHNGNPRY TRVTAMEYLN GQDCSLLLTA TDDGAIRVWK NFADLEKNPE MVTAWQGLSD MLP TTRGAG MVVDWEQETG LLMSSGDVRI VRIWDTDREM KVQDIPTGAD SCVTSLSCDS HRSLIVAGLG DGSIRVYDRR MALS ECRVM TYREHTAWVV KASLQKRPDG HIVSVSVNGD VRIFDPRMPE SVNVLQIVKG LTALDIHPQA DLIACGSVNQ FTAIY NSSG ELINNIKYYD GFMGQRVGAI SCLAFHPHWP HLAVGSNDYY ISVYSVEKRV R |
-Macromolecule #3: Target of rapamycin complex subunit LST8
Macromolecule | Name: Target of rapamycin complex subunit LST8 / 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: 35.91009 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MNTSPGTVGS DPVILATAGY DHTVRFWQAH SGICTRTVQH QDSQVNALEV TPDRSMIAAA GYQHIRMYDL NSNNPNPIIS YDGVNKNIA SVGFHEDGRW MYTGGEDCTA RIWDLRSRNL QCQRIFQVNA PINCVCLHPN QAELIVGDQS GAIHIWDLKT D HNEQLIPE ...String: MNTSPGTVGS DPVILATAGY DHTVRFWQAH SGICTRTVQH QDSQVNALEV TPDRSMIAAA GYQHIRMYDL NSNNPNPIIS YDGVNKNIA SVGFHEDGRW MYTGGEDCTA RIWDLRSRNL QCQRIFQVNA PINCVCLHPN QAELIVGDQS GAIHIWDLKT D HNEQLIPE PEVSITSAHI DPDASYMAAV NSTGNCYVWN LTGGIGDEVT QLIPKTKIPA HTRYALQCRF SPDSTLLATC SA DQTCKIW RTSNFSLMTE LSIKSGNPGE SSRGWMWGCA FSGDSQYIVT ASSDNLARLW CVETGEIKRE YGGHQKAVVC LAF NDSVLG |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.5 mg/mL | ||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: Quantifoil / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR | ||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Dimensions - Width: 7676 pixel / Digitization - Dimensions - Height: 7420 pixel / Digitization - Frames/image: 0-31 / Number real images: 2997 / Average exposure time: 0.25 sec. / Average electron dose: 8.25 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Calibrated defocus max: 2.5 µm / Calibrated defocus min: 1.5 µm / Calibrated magnification: 22500 / Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm / Nominal magnification: 22500 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Protocol: OTHER |
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Output model | PDB-5h64: |