Structure of LRRK2 in Parkinson's disease and model for microtubule interaction.

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) is the most commonly mutated gene in familial Parkinson's disease¹ and is also linked to its idiopathic form². LRRK2 has been proposed to function in membrane trafficking³ and colocalizes with microtubules⁴. Despite the fundamental importance of LRRK2 for understanding and treating Parkinson's disease, structural information on the enzyme is limited. Here we report the structure of the catalytic half of LRRK2, and an atomic model of microtubule-associated LRRK2 built using a reported cryo-electron tomography in situ structure⁵. We propose that the conformation of the LRRK2 kinase domain regulates its interactions with microtubules, with a closed conformation favouring oligomerization on microtubules

SUBMITTER: Deniston CK 

PROVIDER: S-EPMC7726071 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature