[English] 日本語
Yorodumi
- PDB-9om2: Full-length LRRK2 autoinhibited -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9om2
TitleFull-length LRRK2 autoinhibited
ComponentsLeucine-rich repeat serine/threonine-protein kinase 2
KeywordsTRANSFERASE / Kinase / GTPase
Function / homology
Function and homology information


regulation of neuron maturation / 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 / tangential migration from the subventricular zone to the olfactory bulb / regulation of cell projection organization ...regulation of neuron maturation / 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 / tangential migration from the subventricular zone to the olfactory bulb / regulation of cell projection organization / regulation of dopamine receptor signaling pathway / regulation of ER to Golgi vesicle-mediated transport / GTP-dependent protein kinase activity / regulation of SNARE complex assembly / regulation of neuroblast proliferation / protein localization to endoplasmic reticulum exit site / negative regulation of late endosome to lysosome transport / regulation of mitochondrial depolarization / : / peroxidase inhibitor activity / positive regulation of dopamine receptor signaling pathway / amphisome / regulation of synaptic vesicle transport / : / regulation of CAMKK-AMPK signaling cascade / striatum development / negative regulation of autophagosome assembly / co-receptor binding / positive regulation of microglial cell activation / olfactory bulb development / regulation of retrograde transport, endosome to Golgi / negative regulation of GTPase activity / cellular response to curcumin / regulation of locomotion / positive regulation of synaptic vesicle endocytosis / JUN kinase kinase kinase activity / cytoplasmic side of mitochondrial outer membrane / endoplasmic reticulum organization / regulation of cAMP/PKA signal transduction / negative regulation of excitatory postsynaptic potential / multivesicular body, internal vesicle / neuron projection arborization / regulation of dendritic spine morphogenesis / positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / mitochondrion localization / protein localization to mitochondrion / cellular response to dopamine / negative regulation of protein processing / Wnt signalosome / positive regulation of protein autoubiquitination / exploration behavior / GTP metabolic process / regulation of reactive oxygen species metabolic process / regulation of canonical Wnt signaling pathway / lysosome organization / syntaxin-1 binding / positive regulation of programmed cell death / negative regulation of macroautophagy / PTK6 promotes HIF1A stabilization / Golgi-associated vesicle / clathrin binding / regulation of synaptic vesicle exocytosis / locomotory exploration behavior / Golgi organization / regulation of mitochondrial fission / intracellular distribution of mitochondria / Lewy body / protein kinase A binding / canonical Wnt signaling pathway / microvillus / neuromuscular junction development / autolysosome / endoplasmic reticulum exit site / Rho protein signal transduction / determination of adult lifespan / MAP kinase kinase kinase activity / JNK cascade / regulation of synaptic vesicle endocytosis / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / regulation of synaptic transmission, glutamatergic / presynaptic cytosol / cellular response to manganese ion / phagocytic vesicle / neuron projection morphogenesis / positive regulation of autophagy / dendrite cytoplasm / excitatory postsynaptic potential / positive regulation of protein ubiquitination / cellular response to starvation / GTPase activator activity / calcium-mediated signaling / mitochondrion organization / SNARE binding / negative regulation of neuron projection development / cellular response to reactive oxygen species / trans-Golgi network / regulation of protein stability / regulation of membrane potential / tubulin binding / regulation of autophagy
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 / Leucine-rich repeat domain superfamily / Rab subfamily of small GTPases / 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)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.31 Å
AuthorsVillagran-Suarez, A.C. / Bodrug, T.
Funding support United States, 1items
OrganizationGrant numberCountry
Michael J. Fox FoundationASAP-000519 United States
CitationJournal: Cell / Year: 2026
Title: The structural basis for LRRK2's activation and autoinhibition.
Authors: Amalia Villagran Suarez / Kathryn S Hatch / Tatyana Bodrug / Wei Gai / Katherine J Surridge / Elizabeth Moussikhina / Kendrick H V Nguyen / Marta Sanz-Murillo / Robert Callahan / Erica Xiong ...Authors: Amalia Villagran Suarez / Kathryn S Hatch / Tatyana Bodrug / Wei Gai / Katherine J Surridge / Elizabeth Moussikhina / Kendrick H V Nguyen / Marta Sanz-Murillo / Robert Callahan / Erica Xiong / Delisa Ramos / Lawrence Zhu / Verena Dederer / Sebastian Mathea / Janet Iwasa / Stefan Knapp / Kevan M Shokat / Samara L Reck-Peterson / Andres E Leschziner /
Abstract: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the second most common cause of autosomal-dominant Parkinson's disease (PD), and increased LRRK2 kinase activity is also observed in idiopathic ...Mutations in leucine-rich repeat kinase 2 (LRRK2) are the second most common cause of autosomal-dominant Parkinson's disease (PD), and increased LRRK2 kinase activity is also observed in idiopathic PD, making LRRK2 a major actionable therapeutic target. LRRK2 is a 286-kDa multidomain enzyme containing a Ras-like GTPase (ROC) and a kinase domain. Using cryo-electron microscopy (cryo-EM), biochemical reconstitution, and cell-based assays, we show that the ROC GTPase governs switching between autoinhibited and active states: GTP binding promotes activation, whereas GDP binding enforces autoinhibition. Two common PD-linked mutations, G2019S and R1441C/G/H, activate LRRK2 through distinct structural mechanisms, revealing genotype-specific routes to dysregulation. These findings provide a unified framework for understanding LRRK2 regulation with broad therapeutic implications. Stabilizing the guanosine diphosphate (GDP)-bound state may inhibit LRRK2 by maintaining autoinhibition, whereas promoting the GTP-bound state could be advantageous in specific cellular contexts, such as the lung, where increased LRRK2 kinase activity may play protective or regulatory roles.
History
DepositionMay 13, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 12, 2026Provider: repository / Type: Initial release
Revision 1.0Aug 12, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.1Aug 19, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update
Revision 1.1Aug 19, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_PubMed / _citation.title / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)286,9062
Polymers286,4631
Non-polymers4431
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

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


Mass: 286462.781 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LRRK2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q5S007
#2: 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
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: LRRK2-RCKW G2019S bound to GZD-824 and E11 DARPin / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.4
Buffer component
IDConc.NameFormulaBuffer-ID
1150 mMsodium chlorideNaCl1
220 mMHepes1
32.5 mMmagnesium chlroideMgCl21
40.5 mMTCEP1
SpecimenConc.: 0.25 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: 7-12uM LRRK2 with 1.25x of DARPin E11 and 20uM Mli-2
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 130000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 55 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) / Num. of grids imaged: 2 / Num. of real images: 35961 / Details: Final images used 35961

-
Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
2Topazparticle selection
3cryoSPARCimage acquisition
5cryoSPARCCTF correction
8Coot0.9.8.7model fitting
9Rosetta3.13model fitting
11cryoSPARCinitial Euler assignment
12cryoSPARCfinal Euler assignment
14cryoSPARC3D reconstruction
15PHENIX1.2model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 5961012
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.31 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 206812 / Symmetry type: POINT
Atomic model buildingProtocol: OTHER
RefinementHighest resolution: 3.31 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00314262
ELECTRON MICROSCOPYf_angle_d0.63619307
ELECTRON MICROSCOPYf_dihedral_angle_d4.7821902
ELECTRON MICROSCOPYf_chiral_restr0.0422256
ELECTRON MICROSCOPYf_plane_restr0.0052432

+
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