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- PDB-13bv: Cryo-EM structure of human PI3KC3-C1 complex -

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Basic information

Entry
Database: PDB / ID: 13bv
TitleCryo-EM structure of human PI3KC3-C1 complex
Components
  • Beclin 1-associated autophagy-related key regulator
  • Beclin-1
  • Phosphatidylinositol 3-kinase catalytic subunit type 3
  • Phosphoinositide 3-kinase regulatory subunit 4
KeywordsIMMUNE SYSTEM / Lipid kinase / autophagosome formation / signaling protein
Function / homology
Function and homology information


extrinsic component of omegasome membrane / phosphatidylinositol 3-kinase inhibitor activity / extrinsic component of phagophore assembly site membrane / nucleus-vacuole junction / regulation of triglyceride metabolic process / cellular response to aluminum ion / positive regulation of protein lipidation / postsynaptic endosome / Toll Like Receptor 9 (TLR9) Cascade / positive regulation of stress granule assembly ...extrinsic component of omegasome membrane / phosphatidylinositol 3-kinase inhibitor activity / extrinsic component of phagophore assembly site membrane / nucleus-vacuole junction / regulation of triglyceride metabolic process / cellular response to aluminum ion / positive regulation of protein lipidation / postsynaptic endosome / Toll Like Receptor 9 (TLR9) Cascade / positive regulation of stress granule assembly / Synthesis of PIPs at the late endosome membrane / phosphatidylinositol 3-kinase complex, class III / cellular response to oxygen-glucose deprivation / Synthesis of PIPs at the early endosome membrane / phosphatidylinositol 3-kinase complex, class III, type II / phosphatidylinositol 3-kinase complex, class III, type I / response to mitochondrial depolarisation / presynaptic endosome / positive regulation of attachment of mitotic spindle microtubules to kinetochore / host-mediated activation of viral genome replication / mitochondria-associated endoplasmic reticulum membrane contact site / engulfment of apoptotic cell / negative regulation of lysosome organization / phosphatidylinositol kinase activity / Synthesis of PIPs at the Golgi membrane / positive regulation of autophagosome assembly / cytoplasmic side of mitochondrial outer membrane / regulation of protein complex stability / early endosome to late endosome transport / phosphatidylinositol 3-kinase regulator activity / negative regulation of autophagosome assembly / protein localization to phagophore assembly site / response to L-leucine / receptor catabolic process / phagophore assembly site membrane / protein targeting to vacuole / SMAD protein signal transduction / late endosome to vacuole transport / protein targeting to lysosome / endosome organization / pexophagy / positive regulation of natural killer cell mediated cytotoxicity / Translation of Replicase and Assembly of the Replication Transcription Complex / phagophore assembly site / cellular response to nitrogen starvation / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / negative regulation of programmed cell death / post-transcriptional regulation of gene expression / mitotic metaphase chromosome alignment / response to vitamin E / lysosome organization / Macroautophagy / response to iron(II) ion / endosome to lysosome transport / positive regulation of cardiac muscle hypertrophy / autophagosome membrane docking / RSV-host interactions / cytoplasmic pattern recognition receptor signaling pathway / p38MAPK cascade / phosphatidylinositol phosphate biosynthetic process / negative regulation of protein phosphorylation / phosphatidylinositol-mediated signaling / autolysosome / autophagosome membrane / PI3K Cascade / protein secretion / amyloid-beta metabolic process / RHO GTPases Activate NADPH Oxidases / regulation of macroautophagy / autophagosome maturation / cellular defense response / axoneme / neuron development / synaptic vesicle endocytosis / autophagosome assembly / phosphatidylinositol 3-kinase binding / cellular response to glucose starvation / mitophagy / intercellular bridge / phagocytic vesicle / JNK cascade / positive regulation of intrinsic apoptotic signaling pathway / protein-membrane adaptor activity / positive regulation of autophagy / autophagosome / cellular response to epidermal growth factor stimulus / cellular response to copper ion / cellular response to amino acid starvation / cellular response to starvation / regulation of cytokinesis / regulation of autophagy / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / macroautophagy / trans-Golgi network / phosphatidylinositol 3-kinase/protein kinase B signal transduction / circadian rhythm / protein processing / positive regulation of protein phosphorylation
Similarity search - Function
UV radiation resistance protein/autophagy-related protein 14 / Vacuolar sorting 38 and autophagy-related subunit 14 / Serine/threonine-protein kinase Vps15-like / Beclin-1, BH3 domain / Beclin-1 BH3 domain, Bcl-2-interacting / Atg6/Beclin / Atg6/Beclin C-terminal domain superfamily / Atg6, BARA domain / Atg6/beclin, coiled-coil domain / Apg6 BARA domain ...UV radiation resistance protein/autophagy-related protein 14 / Vacuolar sorting 38 and autophagy-related subunit 14 / Serine/threonine-protein kinase Vps15-like / Beclin-1, BH3 domain / Beclin-1 BH3 domain, Bcl-2-interacting / Atg6/Beclin / Atg6/Beclin C-terminal domain superfamily / Atg6, BARA domain / Atg6/beclin, coiled-coil domain / Apg6 BARA domain / Apg6 coiled-coil region / Phosphatidylinositol 3-kinase, Vps34 type / : / : / Phosphatase 2A Regulatory Subunit A, helical domain / HEAT repeat profile. / HEAT, type 2 / C2 phosphatidylinositol 3-kinase-type domain / Phosphoinositide 3-kinase C2 / C2 phosphatidylinositol 3-kinase (PI3K)-type domain profile. / Phosphoinositide 3-kinase, region postulated to contain C2 domain / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase family, accessory domain (PIK domain) / Phosphoinositide 3-kinase, accessory (PIK) domain superfamily / Phosphoinositide 3-kinase, accessory (PIK) domain / Phosphatidylinositol kinase / PIK helical 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 / C2 domain superfamily / Armadillo-like helical / WD domain, G-beta repeat / Armadillo-type fold / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Trp-Asp (WD) repeats signature. / Protein kinase domain / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / Serine/Threonine protein kinases, catalytic domain / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
GUANOSINE-5'-DIPHOSPHATE / MYRISTIC ACID / Beclin-1 / Beclin 1-associated autophagy-related key regulator / Phosphatidylinositol 3-kinase catalytic subunit type 3 / Phosphoinositide 3-kinase regulatory subunit 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.77 Å
AuthorsChen, M. / Hurley, J.H.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS134598 United States
Michael J. Fox FoundationASAP-000350 United States
CitationJournal: To Be Published
Title: Cryo-EM reconstruction of PI3KC3-C2 in complex with Rubicon Middle Region of C terminus
Authors: Chen, M. / Hurley, J.H.
History
DepositionApr 28, 2026Deposition site: RCSB / Processing site: RCSB
SupersessionMay 13, 2026ID: 8SOR
Revision 1.0May 13, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
B: Phosphatidylinositol 3-kinase catalytic subunit type 3
C: Beclin 1-associated autophagy-related key regulator
D: Beclin-1
A: Phosphoinositide 3-kinase regulatory subunit 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)363,0107
Polymers362,3144
Non-polymers6963
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 4 types, 4 molecules BCDA

#1: Protein Phosphatidylinositol 3-kinase catalytic subunit type 3 / PI3-kinase type 3 / PI3K type 3 / PtdIns-3-kinase type 3 / Phosphatidylinositol 3-kinase p100 ...PI3-kinase type 3 / PI3K type 3 / PtdIns-3-kinase type 3 / Phosphatidylinositol 3-kinase p100 subunit / Phosphoinositide-3-kinase class 3 / hVps34


Mass: 101680.328 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3C3, VPS34 / Production host: Homo sapiens (human) / References: UniProt: Q8NEB9, phosphatidylinositol 3-kinase
#2: Protein Beclin 1-associated autophagy-related key regulator


Mass: 55387.266 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ATG14 / Production host: Homo sapiens (human) / References: UniProt: Q6ZNE5
#3: Protein Beclin-1 / Coiled-coil myosin-like BCL2-interacting protein / Protein GT197


Mass: 51953.102 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BECN1, GT197 / Production host: Homo sapiens (human) / References: UniProt: Q14457
#4: Protein Phosphoinositide 3-kinase regulatory subunit 4 / PI3-kinase regulatory subunit 4 / PI3-kinase p150 subunit / Phosphoinositide 3-kinase adaptor protein


Mass: 153293.797 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PIK3R4, VPS15 / Production host: Homo sapiens (human)
References: UniProt: Q99570, non-specific serine/threonine protein kinase

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Non-polymers , 3 types, 3 molecules

#5: Chemical ChemComp-MYR / MYRISTIC ACID


Mass: 228.371 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H28O2 / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O11P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: GDP, energy-carrying molecule*YM
#7: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Human Phosphatidylinositol-3 kinase class III complex I
Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT
Molecular weightValue: 0.36 MDa / Experimental value: YES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
1200 mMSodium chlorideNaCl1
22 mMMagnesium chlorideMgCl21
325 mM4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidHEPES1
41 mMTris(2-carboxyethyl)phosphineTCEP1
SpecimenConc.: 0.45 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1Topaz0.2.5aparticle selection
2SerialEM4.0.20image acquisition
4cryoSPARC4.6.2CTF correction
7Coot0.9.2model fitting
9cryoSPARC4.6.2initial Euler assignment
10cryoSPARC4.6.2final Euler assignment
11cryoSPARC4.6.2classification
12cryoSPARC4.6.23D reconstruction
13PHENIX1.18.2-3874model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.77 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 181267 / Symmetry type: POINT
Atomic model buildingB value: 76.8 / Protocol: FLEXIBLE FIT / Space: REAL
Atomic model buildingPDB-ID: 9MHF
Accession code: 9MHF / Source name: PDB / Type: experimental model
RefinementStereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00416321
ELECTRON MICROSCOPYf_angle_d0.58822053
ELECTRON MICROSCOPYf_dihedral_angle_d6.6562157
ELECTRON MICROSCOPYf_chiral_restr0.0432443
ELECTRON MICROSCOPYf_plane_restr0.0042814

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