[English] 日本語
Yorodumi
- PDB-6oje: Dimeric structure of LRRK2 GTPase domain -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6oje
TitleDimeric structure of LRRK2 GTPase domain
ComponentsLeucine-rich repeat serine/threonine-protein kinase 2
KeywordsHYDROLASE / Parkinson's disease / LRRK2 / GTPase / Dimer / InterSwitch / complex
Function / homology
Function and homology information


peroxidase inhibitor activity / caveola neck / negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation / negative regulation of protein processing involved in protein targeting to mitochondrion / Wnt signalosome assembly / beta-catenin destruction complex binding / regulation of branching morphogenesis of a nerve / regulation of kidney size / regulation of neuron maturation / tangential migration from the subventricular zone to the olfactory bulb ...peroxidase inhibitor activity / caveola neck / negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation / negative regulation of protein processing involved in protein targeting to mitochondrion / Wnt signalosome assembly / beta-catenin destruction complex binding / regulation of branching morphogenesis of a nerve / regulation of kidney size / regulation of neuron maturation / tangential migration from the subventricular zone to the olfactory bulb / protein localization to endoplasmic reticulum exit site / GTP-dependent protein kinase activity / regulation of neuroblast proliferation / regulation of ER to Golgi vesicle-mediated transport / regulation of synaptic vesicle transport / negative regulation of late endosome to lysosome transport / regulation of mitochondrial depolarization / negative regulation of protein targeting to mitochondrion / positive regulation of dopamine receptor signaling pathway / regulation of lysosomal lumen pH / regulation of CAMKK-AMPK signaling cascade / amphisome / mitochondrion localization / cytoplasmic side of mitochondrial outer membrane / co-receptor binding / regulation of retrograde transport, endosome to Golgi / negative regulation of excitatory postsynaptic potential / negative regulation of autophagosome assembly / regulation of dopamine receptor signaling pathway / positive regulation of microglial cell activation / neuron projection arborization / positive regulation of synaptic vesicle endocytosis / JUN kinase kinase kinase activity / olfactory bulb development / regulation of dendritic spine morphogenesis / regulation of protein kinase A signaling / multivesicular body, internal vesicle / striatum development / protein localization to mitochondrion / cellular response to dopamine / presynaptic cytosol / positive regulation of protein autoubiquitination / endoplasmic reticulum organization / positive regulation of programmed cell death / Wnt signalosome / GTP metabolic process / regulation of canonical Wnt signaling pathway / negative regulation of protein processing / syntaxin-1 binding / regulation of reactive oxygen species metabolic process / negative regulation of GTPase activity / autolysosome / protein kinase A binding / exploration behavior / regulation of locomotion / regulation of synaptic vesicle exocytosis / clathrin binding / Golgi-associated vesicle / PTK6 promotes HIF1A stabilization / negative regulation of macroautophagy / neuromuscular junction development / lysosome organization / regulation of mitochondrial fission / intracellular distribution of mitochondria / Golgi organization / positive regulation of nitric-oxide synthase biosynthetic process / locomotory exploration behavior / microvillus / Rho protein signal transduction / endoplasmic reticulum exit site / cellular response to organic cyclic compound / MAP kinase kinase kinase activity / canonical Wnt signaling pathway / positive regulation of protein kinase activity / cellular response to manganese ion / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / positive regulation of autophagy / JNK cascade / regulation of synaptic transmission, glutamatergic / cellular response to starvation / excitatory postsynaptic potential / dendrite cytoplasm / mitochondrion organization / GTPase activator activity / tubulin binding / SNARE binding / neuron projection morphogenesis / negative regulation of protein phosphorylation / negative regulation of protein binding / positive regulation of protein ubiquitination / regulation of membrane potential / regulation of autophagy / determination of adult lifespan / calcium-mediated signaling / mitochondrial membrane / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / peptidyl-threonine phosphorylation / regulation of protein stability / positive regulation of MAP kinase activity / trans-Golgi network
Similarity search - Function
C-terminal of Roc (COR) domain / C-terminal of Roc, COR, domain / Ras of Complex, Roc, domain of DAPkinase / Roc domain profile. / Roc domain / Leucine-rich repeats, bacterial type / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. ...C-terminal of Roc (COR) domain / C-terminal of Roc, COR, domain / Ras of Complex, Roc, domain of DAPkinase / Roc domain profile. / Roc domain / Leucine-rich repeats, bacterial type / Leucine rich repeat / Leucine-rich repeat, typical subtype / Leucine-rich repeats, typical (most populated) subfamily / Leucine-rich repeat profile. / Leucine-rich repeat / Rab subfamily of small GTPases / Leucine-rich repeat domain superfamily / Ankyrin repeat-containing domain superfamily / Armadillo-like helical / Small GTP-binding protein domain / Armadillo-type fold / WD40-repeat-containing domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / WD40/YVTN repeat-like-containing domain superfamily / 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 / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
GUANOSINE-5'-DIPHOSPHATE / Leucine-rich repeat serine/threonine-protein kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.95 Å
AuthorsHoang, Q.Q. / Wu, C.X. / Liao, J. / Park, Y.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)1R01GM111639 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM115844 United States
CitationJournal: To Be Published
Title: Structural basis for conformational plasticity in the GTPase domain of the Parkinson's disease-associated protein LRRK2
Authors: Wu, C.X. / Liao, J. / Park, Y. / Hoang, N.C. / Engel, V.A. / Sanishvili, R. / Takagi, Y. / Johnson, S.M. / Wang, M. / Federici, M. / Nichols, R.J. / Cookson, M.R. / Hoang, Q.Q.
History
DepositionApr 11, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 14, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2023Group: Advisory / Data collection ...Advisory / 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 / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Leucine-rich repeat serine/threonine-protein kinase 2
B: Leucine-rich repeat serine/threonine-protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)48,0068
Polymers47,0222
Non-polymers9846
Water4,324240
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7290 Å2
ΔGint-96 kcal/mol
Surface area18180 Å2
MethodPISA
Unit cell
Length a, b, c (Å)44.647, 103.688, 44.593
Angle α, β, γ (deg.)90.000, 101.200, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Leucine-rich repeat serine/threonine-protein kinase 2 / Dardarin / LRRK2


Mass: 23511.137 Da / Num. of mol.: 2 / Fragment: GTPase domain of leucine-rich repeat kinase 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LRRK2, PARK8 / Plasmid: pETDuet1 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Rosetta2
References: UniProt: Q5S007, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Formula: Mg
#3: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE / Guanosine diphosphate


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C10H15N5O11P2 / Comment: GDP, energy-carrying molecule*YM
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 240 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.15 Å3/Da / Density % sol: 42.88 % / Mosaicity: 1.372 °
Crystal growTemperature: 298 K / Method: microbatch / pH: 6.5 / Details: 100mM KSCN, 25% PEGMME 2000, 0.1M BisTris pH 6.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.0331 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 12, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0331 Å / Relative weight: 1
ReflectionResolution: 1.9→50 Å / Num. obs: 31247 / % possible obs: 98.7 % / Redundancy: 6.1 % / Rmerge(I) obs: 0.072 / Rpim(I) all: 0.031 / Rrim(I) all: 0.078 / Χ2: 1.033 / Net I/σ(I): 5.6 / Num. measured all: 189486
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.9-1.934.30.45714530.8740.2330.5160.74591.7
1.93-1.9750.54614980.8830.2580.6060.51195.4
1.97-2.015.30.41415270.9230.1870.4560.45998
2.01-2.055.40.30115900.9620.1360.3310.46698
2.05-2.0960.27215230.9770.1180.2970.4798.4
2.09-2.146.30.25515940.9740.1080.2780.49299.6
2.14-2.196.40.23215330.9830.0980.2530.48898.7
2.19-2.256.40.30715740.9510.1320.3351.28199
2.25-2.326.40.22415380.980.0950.2440.99699.2
2.32-2.396.20.14115800.9940.060.1530.5699.4
2.39-2.4860.12215810.9920.0540.1340.67199.3
2.48-2.586.40.11315440.9940.0480.1230.7299.5
2.58-2.76.20.09515700.9950.0410.1040.70299.6
2.7-2.846.70.08915970.9940.0370.0970.78499.7
2.84-3.026.60.07515750.9960.0310.0820.99799.6
3.02-3.256.40.07215860.9940.0310.0781.48299.8
3.25-3.586.10.06715770.9940.030.0731.7599.6
3.58-4.096.30.0615890.9970.0260.0662.171100
4.09-5.166.60.05416010.9960.0240.062.058100
5.16-506.20.04916170.9970.0210.0532.19499.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
REFMAC5.8.0253refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: RocCOR domain (3DPU)

3dpu


Resolution: 1.95→43.8 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.95 / WRfactor Rfree: 0.1862 / WRfactor Rwork: 0.1476 / FOM work R set: 0.9024 / SU B: 3.426 / SU ML: 0.049 / SU R Cruickshank DPI: 0.0279 / SU Rfree: 0.0287 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.029 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.1962 1458 5.1 %RANDOM
Rwork0.1603 ---
obs0.1623 27245 99.1 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 140.73 Å2 / Biso mean: 46.293 Å2 / Biso min: 24.31 Å2
Baniso -1Baniso -2Baniso -3
1-8.28 Å20 Å27.23 Å2
2---13.9 Å2-0 Å2
3---5.62 Å2
Refinement stepCycle: final / Resolution: 1.95→43.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2893 0 60 249 3202
Biso mean--31.67 50.91 -
Num. residues----373
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0040.0133097
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172894
X-RAY DIFFRACTIONr_angle_refined_deg1.3661.674202
X-RAY DIFFRACTIONr_angle_other_deg1.21.5966695
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.9215389
X-RAY DIFFRACTIONr_dihedral_angle_2_deg28.55521.892148
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.80615556
X-RAY DIFFRACTIONr_dihedral_angle_4_deg12.9351521
X-RAY DIFFRACTIONr_chiral_restr0.0520.2416
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.023436
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02654
X-RAY DIFFRACTIONr_rigid_bond_restr1.12735991
LS refinement shellResolution: 1.95→2.001 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.079 125 -
Rwork0.069 1924 -
all-2049 -
obs--98.51 %
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)
10.06430.0296-0.0170.0318-0.07750.27530.01250.0131-0.0035-0.00670.00720.00250.0478-0.0085-0.01970.0329-0.002-0.00110.0034-0.00050.0104-11.1665-2.858462.524
20.11520.07460.01260.0678-0.03950.1345-0.01960.0065-0.0227-0.00110.01-0.0218-0.0184-0.02450.00970.01970.00120.00080.00920.00030.01375.843711.713248.4261
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1333 - 1518
2X-RAY DIFFRACTION2B1333 - 1519

+
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