[English] 日本語
Yorodumi
- PDB-5wbh: Structure of the FRB domain of mTOR bound to a substrate recruitm... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5wbh
TitleStructure of the FRB domain of mTOR bound to a substrate recruitment peptide of S6K1
Components
  • Ribosomal protein S6 kinase beta-1Ribosome
  • Serine/threonine-protein kinase mTOR
KeywordsTRANSFERASE
Function / homology
Function and homology information


long-chain fatty acid import into cell / response to electrical stimulus involved in regulation of muscle adaptation / skeletal muscle atrophy / positive regulation of skeletal muscle tissue growth / RNA polymerase III type 2 promoter sequence-specific DNA binding / regulation of glucose import / ribosomal protein S6 kinase activity / positive regulation of cytoplasmic translational initiation / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of pentose-phosphate shunt ...long-chain fatty acid import into cell / response to electrical stimulus involved in regulation of muscle adaptation / skeletal muscle atrophy / positive regulation of skeletal muscle tissue growth / RNA polymerase III type 2 promoter sequence-specific DNA binding / regulation of glucose import / ribosomal protein S6 kinase activity / positive regulation of cytoplasmic translational initiation / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of pentose-phosphate shunt / T-helper 1 cell lineage commitment / 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 / heart valve morphogenesis / regulation of membrane permeability / negative regulation of lysosome organization / RNA polymerase III type 3 promoter sequence-specific DNA binding / TORC1 complex / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / calcineurin-NFAT signaling cascade / regulation of autophagosome assembly / TORC1 signaling / voluntary musculoskeletal movement / regulation of osteoclast differentiation / response to L-leucine / positive regulation of keratinocyte migration / cellular response to L-leucine / MTOR signalling / Amino acids regulate mTORC1 / cellular response to nutrient / energy reserve metabolic process / Energy dependent regulation of mTOR by LKB1-AMPK / nucleus localization / ruffle organization / negative regulation of cell size / cellular response to osmotic stress / phosphatidylinositol-mediated signaling / anoikis / cardiac muscle cell development / positive regulation of transcription by RNA polymerase III / negative regulation of protein localization to nucleus / response to glucagon / regulation of myelination / negative regulation of calcineurin-NFAT signaling cascade / Macroautophagy / regulation of cell size / negative regulation of macroautophagy / lysosome organization / positive regulation of oligodendrocyte differentiation / positive regulation of actin filament polymerization / response to testosterone / positive regulation of myotube differentiation / behavioral response to pain / positive regulation of smooth muscle cell migration / TOR signaling / oligodendrocyte differentiation / mTORC1-mediated signalling / germ cell development / Constitutive Signaling by AKT1 E17K in Cancer / cellular response to nutrient levels / CD28 dependent PI3K/Akt signaling / positive regulation of phosphoprotein phosphatase activity / positive regulation of translational initiation / neuronal action potential / skeletal muscle contraction / HSF1-dependent transactivation / long-term memory / positive regulation of epithelial to mesenchymal transition / regulation of macroautophagy / behavioral fear response / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / response to amino acid / positive regulation of lipid biosynthetic process / response to tumor necrosis factor / response to glucose / phagocytic vesicle / positive regulation of lamellipodium assembly / response to mechanical stimulus / heart morphogenesis / regulation of cellular response to heat / cytoskeleton organization / cardiac muscle contraction / negative regulation of insulin receptor signaling pathway / positive regulation of stress fiber assembly / positive regulation of TORC1 signaling / cellular response to amino acid starvation / T cell costimulation / cellular response to starvation / protein serine/threonine/tyrosine kinase activity / positive regulation of glycolytic process / cellular response to dexamethasone stimulus / positive regulation of mitotic cell cycle / response to nutrient levels / post-embryonic development / response to nutrient / negative regulation of autophagy
Similarity search - Function
FKBP12-rapamycin binding domain / Ribosomal protein S6 kinase / Domain of unknown function DUF3385, target of rapamycin protein / Domain of unknown function (DUF3385) / Domain of unknown function / FKBP12-rapamycin binding domain / Serine/threonine-protein kinase TOR / FKBP12-rapamycin binding domain superfamily / FKBP12-rapamycin binding domain / Rapamycin binding domain ...FKBP12-rapamycin binding domain / Ribosomal protein S6 kinase / Domain of unknown function DUF3385, target of rapamycin protein / Domain of unknown function (DUF3385) / Domain of unknown function / FKBP12-rapamycin binding domain / Serine/threonine-protein kinase TOR / FKBP12-rapamycin binding domain superfamily / FKBP12-rapamycin binding domain / Rapamycin binding domain / Protein kinase, C-terminal / Protein kinase C terminal domain / PIK-related kinase, FAT / FAT domain / FATC domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / Four Helix Bundle (Hemerythrin (Met), subunit A) / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / Armadillo-type fold / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Ribosomal protein S6 kinase beta-1 / Serine/threonine-protein kinase mTOR
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.75 Å
AuthorsPavletich, N.P. / Yang, H.
CitationJournal: Nature / Year: 2017
Title: Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.
Authors: Haijuan Yang / Xiaolu Jiang / Buren Li / Hyo J Yang / Meredith Miller / Angela Yang / Ankita Dhar / Nikola P Pavletich /
Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the ...The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.
History
DepositionJun 29, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 20, 2017Provider: repository / Type: Initial release
Revision 1.1Apr 18, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase mTOR
B: Serine/threonine-protein kinase mTOR
C: Serine/threonine-protein kinase mTOR
D: Serine/threonine-protein kinase mTOR
E: Serine/threonine-protein kinase mTOR
W: Ribosomal protein S6 kinase beta-1


Theoretical massNumber of molelcules
Total (without water)63,5166
Polymers63,5166
Non-polymers00
Water6,017334
1
A: Serine/threonine-protein kinase mTOR


Theoretical massNumber of molelcules
Total (without water)12,0921
Polymers12,0921
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area6100 Å2
MethodPISA
2
B: Serine/threonine-protein kinase mTOR


Theoretical massNumber of molelcules
Total (without water)12,0921
Polymers12,0921
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area5770 Å2
MethodPISA
3
C: Serine/threonine-protein kinase mTOR


Theoretical massNumber of molelcules
Total (without water)12,0921
Polymers12,0921
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area6360 Å2
MethodPISA
4
D: Serine/threonine-protein kinase mTOR
W: Ribosomal protein S6 kinase beta-1


Theoretical massNumber of molelcules
Total (without water)15,1492
Polymers15,1492
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area880 Å2
ΔGint-8 kcal/mol
Surface area7320 Å2
MethodPISA
5
E: Serine/threonine-protein kinase mTOR


Theoretical massNumber of molelcules
Total (without water)12,0921
Polymers12,0921
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area6450 Å2
MethodPISA
Unit cell
Length a, b, c (Å)60.613, 80.944, 134.848
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP22121

-
Components

#1: Protein
Serine/threonine-protein kinase mTOR / FK506-binding protein 12-rapamycin complex-associated protein 1 / FKBP12-rapamycin complex- ...FK506-binding protein 12-rapamycin complex-associated protein 1 / FKBP12-rapamycin complex-associated protein / Mammalian target of rapamycin / mTOR / Mechanistic target of rapamycin / Rapamycin and FKBP12 target 1 / Rapamycin target protein 1


Mass: 12091.749 Da / Num. of mol.: 5 / Fragment: residues 2018-2114
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MTOR, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 / Plasmid: pET26 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: P42345, non-specific serine/threonine protein kinase
#2: Protein/peptide Ribosomal protein S6 kinase beta-1 / Ribosome / S6K1 / 70 kDa ribosomal protein S6 kinase 1 / p70-S6K 1 / Ribosomal protein S6 kinase I / ...S6K1 / 70 kDa ribosomal protein S6 kinase 1 / p70-S6K 1 / Ribosomal protein S6 kinase I / Serine/threonine-protein kinase 14A / p70 ribosomal S6 kinase alpha / p70 S6KA


Mass: 3057.544 Da / Num. of mol.: 1 / Fragment: residues 412-437
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RPS6KB1, STK14A / Plasmid: pET26 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: P23443, non-specific serine/threonine protein kinase
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 334 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.77 Å3/Da / Density % sol: 55.58 % / Mosaicity: 0.738 °
Crystal growTemperature: 289 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: tacsimate

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-C / Wavelength: 0.9792 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Feb 12, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 1.75→50 Å / Num. obs: 66487 / % possible obs: 98.2 % / Redundancy: 4.9 % / Rmerge(I) obs: 0.068 / Rpim(I) all: 0.032 / Rrim(I) all: 0.076 / Χ2: 1.575 / Net I/σ(I): 11.6 / Num. measured all: 328879
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.75-1.8140.603615361530.7270.3040.680.89292.4
1.81-1.894.50.48964840.8460.240.5470.96297.1
1.89-1.974.80.39166280.9110.190.4361.16898.8
1.97-2.075.30.27766790.950.1290.3071.2299.8
2.07-2.25.20.18166990.9780.0850.21.30799.8
2.2-2.384.80.13266510.9850.0650.1481.59898.9
2.38-2.615.40.09867550.9930.0450.1081.60699.8
2.61-2.9950.07267090.9960.0340.081.91599.1
2.99-3.775.30.05367900.9970.0240.0582.46698.9
3.77-5050.0469390.9980.0190.0452.21497.3

-
Processing

Software
NameVersionClassification
SCALEPACKdata scaling
REFMAC5.8.0158refinement
PDB_EXTRACT3.22data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1FAP

1fap


Resolution: 1.75→50.01 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.955 / SU B: 7.489 / SU ML: 0.102 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.111 / ESU R Free: 0.102
Details: U VALUES : WITH TLS ADDED HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
RfactorNum. reflection% reflectionSelection details
Rfree0.2102 1932 3 %RANDOM
Rwork0.1931 ---
obs0.1937 61680 93.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 130.28 Å2 / Biso mean: 37.909 Å2 / Biso min: 12.88 Å2
Baniso -1Baniso -2Baniso -3
1--3.8 Å2-0 Å20 Å2
2--5.45 Å2-0 Å2
3----1.65 Å2
Refinement stepCycle: final / Resolution: 1.75→50.01 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4108 0 0 334 4442
Biso mean---46.87 -
Num. residues----485
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0194221
X-RAY DIFFRACTIONr_bond_other_d0.0010.023936
X-RAY DIFFRACTIONr_angle_refined_deg1.0661.9275667
X-RAY DIFFRACTIONr_angle_other_deg0.8923.0018963
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.9515479
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.31523.203231
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.09815775
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.4591535
X-RAY DIFFRACTIONr_chiral_restr0.0650.2546
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.024722
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021069
LS refinement shellResolution: 1.75→1.795 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.353 119 -
Rwork0.36 3649 -
all-3768 -
obs--76.04 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
12.1130.68472.30891.20040.46224.0271-0.0189-0.211-0.03020.06910.057-0.0650.0685-0.0158-0.0380.26340.02320.0230.1826-0.01540.2078-12.42721.397-8.094
25.8582-0.7562-1.4490.66140.14662.2255-0.096-0.0385-0.1363-0.05170.0513-0.04560.06920.04950.04470.28970.0062-0.00620.14260.01690.183717.68321.7311.004
35.56670.26611.74761.53260.27831.407-0.0198-0.19180.3220.1001-0.01170.0533-0.1230.03620.03150.31330.01340.01530.0207-0.0140.2910.278-0.195-30.097
42.7379-0.1032-1.9592.0190.40814.29840.01070.10640.0413-0.0372-0.0136-0.08460.0451-0.02130.00290.2380.0011-0.02830.00590.01230.1522-9.86817.854-39.42
53.72060.2751-1.25081.5949-0.72582.2012-0.0317-0.062-0.1385-0.0071-0.03140.11280.08350.20280.06320.29250.030.00050.03750.0150.30420.01133.968-30.867
61.4125-3.11972.46278.9162-5.77354.46950.17350.0981-0.2394-0.35350.02830.18020.25430.0643-0.20170.30990.0219-0.00440.2324-0.06680.3799-10.9635.581-48.758
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A2023 - 2116
2X-RAY DIFFRACTION2B2023 - 2116
3X-RAY DIFFRACTION3C2019 - 2116
4X-RAY DIFFRACTION4D2023 - 2116
5X-RAY DIFFRACTION5E2023 - 2116
6X-RAY DIFFRACTION6W392 - 410

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more