ArticleNature communications2017
A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 461 citations in OpenAlex.
- Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.Journal of translational medicine · 2025Pooled it
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- R1398 is the GTP-γ-phosphate sensor that drives the ROC G-domain switching mechanism unique to Parkinson's disease-associated LRRK2.Research square · 2026Article
- LRRK2 regulates ArfGAP1 membrane localization, activity and neuronal toxicity via phosphorylation within its lipid-sensing ALPS2 motif.bioRxiv : the preprint server for biology · 2026Article
- LRRK2 regulates ArfGAP1 membrane localization, activity and neuronal integrity via phosphorylation within its lipid-sensing ALPS2 motif.Frontiers in molecular neuroscience · 2026Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Affective phenotypes in heterozygousFrontiers in genetics · 2025Article
- Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism.eLife · 2024Article
- CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.Science advances · 2024Article
- LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.Trends in molecular medicine · 2024Review
- Article
- LRRK2 Structure-Based Activation Mechanism and Pathogenesis.Biomolecules · 2023Review
- Roc, the G-domain of the Parkinson's disease-associated protein LRRK2.Trends in biochemical sciences · 2022Review
- Homodimerized cytoplasmic domain of PD-L1 regulates its complex glycosylation in living cells.Communications biology · 2022Article
- Review
- Nanobodies as allosteric modulators of Parkinson's disease-associated LRRK2.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease.Translational neurodegeneration · 2022Review
- Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.Bioscience reports · 2021Review
- Markov State Models and Molecular Dynamics Simulations Provide Understanding of the Nucleotide-Dependent Dimerization-Based Activation of LRRK2 ROC Domain.Molecules (Basel, Switzerland) · 2021Article
- From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease.The Biochemical journal · 2021Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is regulated. Here, we show that oligomerization of a homologous bacterial Roco protein depends on the nucleotide load. The protein is mainly dimeric in the nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding, leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD-associated mutation stabilizes the dimer and decreases the GTPase activity. This work thus provides insights into the conformational cycle of Roco proteins and suggests a link between oligomerization and disease-associated mutations in LRRK2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.