[English] 日本語
Yorodumi
- PDB-6xaf: 1.9A crystal structure of the GTPase domain of Parkinson's diseas... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6xaf
Title1.9A crystal structure of the GTPase domain of Parkinson's disease-associated protein LRRK2 carrying R1398H
ComponentsLeucine-rich repeat serine/threonine-protein kinase 2
KeywordsHYDROLASE / Parkinson's disease / LRRK2 / GTPase / Dimer / InterSwitch / complex
Function / homology
Function and homology information


caveola neck / : / beta-catenin destruction complex binding / regulation of branching morphogenesis of a nerve / Wnt signalosome assembly / negative regulation of motile cilium assembly / regulation of kidney size / regulation of cell projection organization / tangential migration from the subventricular zone to the olfactory bulb / GTP-dependent protein kinase activity ...caveola neck / : / beta-catenin destruction complex binding / regulation of branching morphogenesis of a nerve / Wnt signalosome assembly / negative regulation of motile cilium assembly / regulation of kidney size / regulation of cell projection organization / tangential migration from the subventricular zone to the olfactory bulb / GTP-dependent protein kinase activity / regulation of SNARE complex assembly / regulation of neuroblast proliferation / regulation of ER to Golgi vesicle-mediated transport / protein localization to endoplasmic reticulum exit site / peroxidase inhibitor activity / negative regulation of late endosome to lysosome transport / regulation of mitochondrial depolarization / : / positive regulation of dopamine receptor signaling pathway / amphisome / regulation of synaptic vesicle transport / : / regulation of CAMKK-AMPK signaling cascade / co-receptor binding / negative regulation of GTPase activity / regulation of dopamine receptor signaling pathway / cellular response to curcumin / positive regulation of microglial cell activation / regulation of retrograde transport, endosome to Golgi / regulation of neuron maturation / cytoplasmic side of mitochondrial outer membrane / negative regulation of autophagosome assembly / olfactory bulb development / positive regulation of synaptic vesicle endocytosis / regulation of cAMP/PKA signal transduction / JUN kinase kinase kinase activity / multivesicular body, internal vesicle / negative regulation of excitatory postsynaptic potential / striatum development / neuron projection arborization / regulation of dendritic spine morphogenesis / mitochondrion localization / protein localization to mitochondrion / cellular response to dopamine / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / endoplasmic reticulum organization / positive regulation of protein autoubiquitination / negative regulation of protein processing / Wnt signalosome / positive regulation of programmed cell death / GTP metabolic process / regulation of canonical Wnt signaling pathway / syntaxin-1 binding / regulation of reactive oxygen species metabolic process / Golgi-associated vesicle / PTK6 promotes HIF1A stabilization / negative regulation of macroautophagy / lysosome organization / clathrin binding / regulation of mitochondrial fission / Lewy body / regulation of locomotion / intracellular distribution of mitochondria / regulation of synaptic vesicle exocytosis / protein kinase A binding / neuromuscular junction development / Golgi organization / microvillus / autolysosome / exploration behavior / locomotory exploration behavior / endoplasmic reticulum exit site / negative regulation of Notch signaling pathway / MAP kinase kinase kinase activity / regulation of synaptic vesicle endocytosis / canonical Wnt signaling pathway / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / regulation of synaptic transmission, glutamatergic / Rho protein signal transduction / presynaptic cytosol / phagocytic vesicle / neuron projection morphogenesis / JNK cascade / cellular response to manganese ion / positive regulation of autophagy / dendrite cytoplasm / cellular response to starvation / positive regulation of protein ubiquitination / GTPase activator activity / determination of adult lifespan / regulation of autophagy / SNARE binding / cellular response to reactive oxygen species / mitochondrion organization / trans-Golgi network / excitatory postsynaptic potential / calcium-mediated signaling / regulation of protein stability / regulation of membrane potential / tubulin binding
Similarity search - Function
: / : / : / LRRK2 ARM repeat / LRRK2 ANK repeat / LRRK2 beta propeller / : / : / C-terminal of Roc, COR-B domain / C-terminal of Roc (COR) domain ...: / : / : / LRRK2 ARM repeat / LRRK2 ANK repeat / LRRK2 beta propeller / : / : / C-terminal of Roc, COR-B domain / C-terminal of Roc (COR) domain / C-terminal of Roc, COR-A 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 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / 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 / Resolution: 1.968 Å
AuthorsHoang, Q.Q. / Liao, J. / Huang, X. / Park, Y. / Wu, C.X.
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
DepositionJun 4, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 9, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 18, 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: 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)47,6876
Polymers46,7522
Non-polymers9354
Water2,414134
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6820 Å2
ΔGint-74 kcal/mol
Surface area16240 Å2
MethodPISA
Unit cell
Length a, b, c (Å)44.497, 101.785, 44.527
Angle α, β, γ (deg.)90.000, 101.380, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

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


Mass: 23375.887 Da / Num. of mol.: 2 / Fragment: GTPase domain (UNP residues 1329-1520) / Mutation: R1398H, K1460A, K1463A
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, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#2: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GDP / GUANOSINE-5'-DIPHOSPHATE


Type: RNA linking / Mass: 443.201 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H15N5O11P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: GDP, energy-carrying molecule*YM
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 134 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.11 Å3/Da / Density % sol: 41.83 %
Crystal growTemperature: 298 K / Method: microbatch / pH: 6.5
Details: 100 mM potassium thiocyanate, 25% PEG2000 MME, 0.1 M Bis-Tris, pH 6.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 7, 2018
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.96→20.05 Å / Num. obs: 27384 / % possible obs: 99.35 % / Redundancy: 3.3 % / Biso Wilson estimate: 29.64 Å2 / CC1/2: 0.968 / Rpim(I) all: 0.062 / Rrim(I) all: 0.115 / Net I/σ(I): 13.64
Reflection shellResolution: 1.96→1.99 Å / Num. unique obs: 2565 / CC1/2: 0.862

-
Processing

Software
NameVersionClassification
PHENIX1.13_2998refinement
HKL-2000data scaling
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 6OJF

6ojf


Resolution: 1.968→20.048 Å / SU ML: 0.19 / Cross valid method: THROUGHOUT / σ(F): 1.38 / Phase error: 24.04 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2214 1998 7.3 %
Rwork0.1804 25382 -
obs0.1834 27380 99.34 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 135.65 Å2 / Biso mean: 43.7206 Å2 / Biso min: 16.77 Å2
Refinement stepCycle: final / Resolution: 1.968→20.048 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2684 0 58 134 2876
Biso mean--27.99 40.72 -
Num. residues----346
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.968-2.01670.25131370.1968175495
2.0167-2.07110.25611330.1971177899
2.0711-2.1320.2471470.19451842100
2.132-2.20080.25911390.20121787100
2.2008-2.27930.21851440.18081820100
2.2793-2.37040.24521440.1741823100
2.3704-2.47810.23141410.18211836100
2.4781-2.60850.24281440.18321805100
2.6085-2.77160.26541430.20261831100
2.7716-2.98490.22561440.19761821100
2.9849-3.28410.24371440.19111807100
3.2841-3.75660.21041460.17371834100
3.7566-4.72270.17131430.15271810100
4.7227-20.0480.21711490.1815183499
Refinement TLS params.Method: refined / Origin x: 10.0919 Å / Origin y: -5.4809 Å / Origin z: 9.5039 Å
111213212223313233
T0.227 Å20.0258 Å2-0.0273 Å2-0.1809 Å2-0.0154 Å2--0.2086 Å2
L2.4513 °20.7327 °2-1.0519 °2-1.0303 °2-0.6779 °2--1.9019 °2
S0.0081 Å °0.1244 Å °0.1014 Å °-0.0031 Å °0.0114 Å °0.0007 Å °-0.0103 Å °-0.1254 Å °-0.0116 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA1335 - 1514
2X-RAY DIFFRACTION1allB1334 - 1515
3X-RAY DIFFRACTION1allD1 - 2
4X-RAY DIFFRACTION1allC1 - 2
5X-RAY DIFFRACTION1allS1 - 133
6X-RAY DIFFRACTION1allS134

+
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