A homologue of the Parkinson’s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover

• DOI: 10.1038/s41467-017-01103-4
• Publication Date: 2017-10-12T10:25:46Z
• Authors: Egon Deyaert; Lina Wauters; Giambattista Guai...; Albert Konijnenberg; Margaux Leemans; Susanne Terheyden; Arsen Petrovic; Rodrigo Gallardo; Laura M. Nedervee...; Panagiotis S. Ath...; Henderikus Pots; Peter J. M. Van H...; Frank Sobott; Christian Johanne...; Rouslan Efremov; Arjan Kortholt; Wim Versées
• Keywords: LRRK2

Abstract Mutations in LRRK2 are a common cause of genetic Parkinson’s disease (PD). is multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with bacterial homologue, was proposed to act as activated by dimerization (GAD), while recent reports suggest exist under monomeric dimeric form vivo. It however unknown how oligomerization regulated. Here, we show that homologous protein depends on the nucleotide load. The mainly nucleotide-free GDP-bound states, it forms monomers upon GTP binding, leading monomer-dimer cycle during hydrolysis. An analogue PD-associated mutation stabilizes dimer decreases This work thus provides insights into conformational proteins suggests link between disease-associated mutations LRRK2.