ArticleScientific reports2017
Cryo-EM analysis of homodimeric full-length LRRK2 and LRRK1 protein complexes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- 14-3-3 binding maintains the Parkinson's associated kinase LRRK2 in an inactive state.Nature communications · 2025Article
- Review
- Structure of LRRK1 and mechanisms of autoinhibition and activation.Nature structural & molecular biology · 2023Article
- Structure and regulation of full-length human leucine-rich repeat kinase 1.Nature communications · 2023Article
- Perspective on the current state of the LRRK2 field.NPJ Parkinson's disease · 2023Review
- LRRK2 Structure-Based Activation Mechanism and Pathogenesis.Biomolecules · 2023Review
- PAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation.Frontiers in molecular neuroscience · 2023Article
- PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain.The Biochemical journal · 2022Article
- The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.The Journal of cell biology · 2022Article
- Article
- WDR37 syndrome: identification of a distinct new cluster of disease-associated variants and functional analyses of mutant proteins.Human genetics · 2021Article
- Structural Biology of LRRK2 and its Interaction with Microtubules.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.Bioscience reports · 2021Review
- The Regulation of Rab GTPases by Phosphorylation.Biomolecules · 2021Review
- From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease.The Biochemical journal · 2021Article
- LRRK2 Targeting Strategies as Potential Treatment of Parkinson's Disease.Biomolecules · 2021Review
- Article
- Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms.The Biochemical journal · 2021Article
- Article
- Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain protein implicated in the pathogenesis of both familial and sporadic Parkinson's disease (PD), and currently one of the most promising therapeutic targets for drug design in Parkinson's disease. In contrast, LRRK1, the closest homologue to LRRK2, does not play any role in PD. Here, we use cryo-electron microscopy (cryo-EM) and single particle analysis to gain structural insight into the full-length dimeric structures of LRRK2 and LRRK1. Differential scanning fluorimetry-based screening of purification buffers showed that elution of the purified LRRK2 protein in a high pH buffer is beneficial in obtaining high quality cryo-EM images. Next, analysis of the 3D maps generated from the cryo-EM data show 16 and 25 Å resolution structures of full length LRRK2 and LRRK1, respectively, revealing the overall shape of the dimers with two-fold symmetric orientations of the protomers that is closely similar between the two proteins. These results suggest that dimerization mechanisms of both LRRKs are closely related and hence that specificities in functions of each LRRK are likely derived from LRRK2 and LRRK1's other biochemical functions. To our knowledge, this study is the first to provide 3D structural insights in LRRK2 and LRRK1 dimers in parallel.
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