ReviewFrontiers in molecular neuroscience2014
Structural biology of the LRRK2 GTPase and kinase domains: implications for regulation.
Review in Frontiers in molecular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 82 citations in OpenAlex.
- Regulation between LRRK2 and PP2A signaling in cellular models of Parkinson's disease.The Biochemical journal · 2026Article
- Parkinson's disease: genetics and neuroinflammatory insights.Inflammopharmacology · 2025Review
- 14-3-3 binding maintains the Parkinson's associated kinase LRRK2 in an inactive state.Nature communications · 2025Article
- Multifactorial etiology of progressive supranuclear palsy (PSP): the genetic component.Acta neuropathologica · 2025Review
- The Leucine-Rich Repeat Kinase 2 Variant LRRK2International journal of molecular sciences · 2025Article
- Article
- LRRK2 and Parkinson's disease: from genetics to targeted therapy.Annals of clinical and translational neurology · 2023Review
- LRRK2 Structure-Based Activation Mechanism and Pathogenesis.Biomolecules · 2023Review
- Structural Insights and Development of LRRK2 Inhibitors for Parkinson's Disease in the Last Decade.Genes · 2022Review
- High-Throughput Sequencing Haplotype Analysis Indicates inLife (Basel, Switzerland) · 2022Article
- Genetic and Environmental Factors Influence the Pleomorphy ofInternational journal of molecular sciences · 2021Review
- Predicting host dependency factors of pathogens inComputational and structural biotechnology journal · 2021Article
- Elevated In Vitro Kinase Activity in Peripheral Blood Mononuclear Cells of Leucine-Rich Repeat Kinase 2 G2019S Carriers: A Novel Enzyme-Linked Immunosorbent Assay-Based Method.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- Analysis of rare variants of autosomal-dominant genes in a Chinese population with sporadic Parkinson's disease.Molecular genetics & genomic medicine · 2020Article
- Sequential screening nominates the Parkinson's disease associated kinase LRRK2 as a regulator of Clathrin-mediated endocytosis.Neurobiology of disease · 2020Article
- Advances in elucidating the function of leucine-rich repeat protein kinase-2 in normal cells and Parkinson's disease.Current opinion in cell biology · 2020Review
- LRRK2 regulates endoplasmic reticulum-mitochondrial tethering through the PERK-mediated ubiquitination pathway.The EMBO journal · 2020Article
- Leucine Rich Repeat Kinase 2 and Innate Immunity.Frontiers in neuroscience · 2020Review
- PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins.eLife · 2019Article
- Roco Proteins: GTPases with a Baroque Structure and Mechanism.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human leucine rich repeat kinase 2 (LRRK2) belongs to the Roco family of proteins, which are characterized by the presence of a Ras-like G-domain (Roc), a C-terminal of Roc domain (COR), and a kinase domain. Mutations in LRRK2 have been found to be thus far the most frequent cause of late-onset Parkinson's disease (PD). Several of the pathogenic mutations in LRRK2 result in decreased GTPase activity and enhanced kinase activity, suggesting a possible PD-related gain of abnormal function. Important progress in the structural understanding of LRRK2 has come from our work with related Roco proteins from lower organisms. Atomic structures of Roco proteins from prokaryotes revealed that Roco proteins belong to the GAD class of molecular switches (G proteins activated by nucleotide dependent dimerization). As in LRRK2, PD-analogous mutations in Roco proteins from bacteria decrease the GTPase reaction. Studies with Roco proteins from the model organism Dictyostelium discoideum revealed that PD mutants have different effects and most importantly they explained the G2019S-related increased LRRK2 kinase activity. Furthermore, the structure of Dictyostelium Roco4 kinase in complex with the LRRK2 inhibitor H1152 showed that Roco4 and other Roco family proteins can be important for the optimization of the current, and identification of new, LRRK2 kinase inhibitors. In this review we highlight the recent progress in structural and biochemical characterization of Roco proteins and discuss its implication for the understanding of the complex regulatory mechanism of LRRK2.
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