Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	The structural basis for LRRK2's activation and autoinhibition.
Journal, issue, pages	Cell, Year 2026
Publish date	Aug 10, 2026
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 /
PubMed 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.
External links	Cell / PubMed:42575089
Methods	EM (single particle)
Resolution	3.15 - 3.72 Å
Structure data	70604 9om2 EMDB-70604, PDB-9om2: Full-length LRRK2 autoinhibited Method: EM (single particle) / Resolution: 3.31 Å 70981 9oxh EMDB-70981, PDB-9oxh: Full length LRRK2 bound to G10 DARPin Method: EM (single particle) / Resolution: 3.15 Å 70982 9oxi EMDB-70982, PDB-9oxi: Full-length LRRK2 autonhibited (flexible) Method: EM (single particle) / Resolution: 3.72 Å 71012 9oya EMDB-71012, PDB-9oya: Full LRRK2 (R1441C mutant) after symmetry expansion Method: EM (single particle) / Resolution: 3.44 Å 72555 9y67 EMDB-72555, PDB-9y67: Full length LRRK2 after symmetry expansion Method: EM (single particle) / Resolution: 3.72 Å 72556 9y68 EMDB-72556, PDB-9y68: Full length LRRK2 (G2019S) after symmetry expansion Method: EM (single particle) / Resolution: 3.25 Å 73338 9yqk EMDB-73338, PDB-9yqk: C-terminal LRRK2 bound to C12 DARPin Method: EM (single particle) / Resolution: 3.6 Å
Chemicals	ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying moleculeYM ChemComp-MG*: Unknown entry
Source	homo sapiens (human) synthetic construct (others)
Keywords	TRANSFERASE / Kinase / GTPase / STRUCTURAL PROTEIN / Complex / GTPases / HYDROLASE / LRRK2 / PROTEIN BINDING / DARPins