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Open data
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Basic information
Entry | Database: PDB / ID: 800000 | |||||||||||||||
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Title | Structure of dimeric LRRK1 | |||||||||||||||
![]() | Leucine-rich repeat serine/threonine-protein kinase 1 | |||||||||||||||
![]() | TRANSFERASE / dimer | |||||||||||||||
Function / homology | ![]() negative regulation of peptidyl-tyrosine phosphorylation / positive regulation of intracellular signal transduction / osteoclast development / bone resorption / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of canonical Wnt signaling pathway / non-specific serine/threonine protein kinase / intracellular signal transduction / phosphorylation / protein serine kinase activity ...negative regulation of peptidyl-tyrosine phosphorylation / positive regulation of intracellular signal transduction / osteoclast development / bone resorption / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of canonical Wnt signaling pathway / non-specific serine/threonine protein kinase / intracellular signal transduction / phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / GTP binding / mitochondrion / ATP binding / membrane / identical protein binding / metal ion binding / cytosol Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.6 Å | |||||||||||||||
![]() | Reimer, J.M. / Lin, Y.X. / Leschziner, A.E. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure of LRRK1 and mechanisms of autoinhibition and activation. Authors: Janice M Reimer / Andrea M Dickey / Yu Xuan Lin / Robert G Abrisch / Sebastian Mathea / Deep Chatterjee / Elizabeth J Fay / Stefan Knapp / Matthew D Daugherty / Samara L Reck-Peterson / Andres E Leschziner / ![]() ![]() Abstract: Leucine Rich Repeat Kinase 1 and 2 (LRRK1 and LRRK2) are homologs in the ROCO family of proteins in humans. Despite their shared domain architecture and involvement in intracellular trafficking, ...Leucine Rich Repeat Kinase 1 and 2 (LRRK1 and LRRK2) are homologs in the ROCO family of proteins in humans. Despite their shared domain architecture and involvement in intracellular trafficking, their disease associations are strikingly different: LRRK2 is involved in familial Parkinson's disease while LRRK1 is linked to bone diseases. Furthermore, Parkinson's disease-linked mutations in LRRK2 are typically autosomal dominant gain-of-function while those in LRRK1 are autosomal recessive loss-of-function. Here, to understand these differences, we solved cryo-EM structures of LRRK1 in its monomeric and dimeric forms. Both differ from the corresponding LRRK2 structures. Unlike LRRK2, which is sterically autoinhibited as a monomer, LRRK1 is sterically autoinhibited in a dimer-dependent manner. LRRK1 has an additional level of autoinhibition that prevents activation of the kinase and is absent in LRRK2. Finally, we place the structural signatures of LRRK1 and LRRK2 in the context of the evolution of the LRRK family of proteins. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 620.9 KB | Display | ![]() |
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PDB format | ![]() | 500 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 93.8 KB | Display | |
Data in CIF | ![]() | 140.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 27817MC ![]() 8e04C ![]() 8e06C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 225739.219 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q38SD2, non-specific serine/threonine protein kinase #2: Chemical | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Full length LRRK1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2124 nm / Nominal defocus min: 1263 nm |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 58913 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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