Publication
A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover
Deyaert, E., Wauters, L., Guaitoli, G., Konijnenberg, A., Leemans, M., Terheyden, S., Petrovic, A., Gallardo, R., Nederveen-Schippers, L. M., Athanasopoulos, P. S., Pots, H., Van Haastert, P. J. M., Sobott, F., Gloeckner, C. J., Efremov, R., Kortholt, A. & Versées, W., 18-Oct-2017, In : Nature Communications. 8, 1, p. 1-12 12 p., 1008.Research output: Contribution to journal › Article › Academic › peer-review

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- A homologue of the Parkinson ’ s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnove
Final publisher's version, 3.88 MB, PDF document
DOI
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.
Original language | English |
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Article number | 1008 |
Pages (from-to) | 1-12 |
Number of pages | 12 |
Journal | Nature Communications |
Volume | 8 |
Issue number | 1 |
Publication status | Published - 18-Oct-2017 |
- Parkinson's disease, LRRK2, protein conformation, transition, GTP-binding
Keywords
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