Proximity proteomics reveals a co-evolved LRRK2-regulatory network linked to centrosomes

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) not only plays a vital role in familial forms of Parkinson's disease (PD) but also represents a risk factor for idiopathic PD. Its multi-domain architecture enables fine-tuned regulation of its biological function by orchestrating intra- and intermolecular interactions. Here, we present BioID proximity proteomes of LRRK2 that reveal new interactors, which we further characterize using a novel evolutionary and structural bioinformatics pipeline. Co-evolutionary analysis of the protein-protein interaction network identifies a structural and functional module enriched in cytoskeletal components associated with the centrosome and microtubules. In addition, structural modelling of binary interactions using AlphaFold-Multimer reveals distinct groups of intera

SUBMITTER: Marita Eckert 

PROVIDER: S-SCDT-10_1038-S44319-026-00806-4 | biostudies-other |

REPOSITORIES: biostudies-other