| dc.creator |
Van Haastert, Peter J. M. |
|
| dc.creator |
Deyaert, Egon |
|
| dc.creator |
Wauters, Lina |
|
| dc.creator |
Guaitoli, Giambattista |
|
| dc.creator |
Konijnenberg, Albert |
|
| dc.creator |
Leemans, Margaux |
|
| dc.creator |
Terheyden, Susanne |
|
| dc.creator |
Petrovic, Arsen |
|
| dc.creator |
Gallardo, Rodrigo |
|
| dc.creator |
Nederveen-Schippers, Laura M. |
|
| dc.creator |
Athanasopoulos, Panagiotis S. |
|
| dc.creator |
Pots, Henderikus |
|
| dc.creator |
Sobott, Frank |
|
| dc.creator |
Gloeckner, Christian Johannes |
|
| dc.creator |
Efremov, Rouslan |
|
| dc.creator |
Kortholt, Arjan |
|
| dc.creator |
Versees, Wim |
|
| dc.date |
2017-10-01T00:00:00Z |
|
| dc.date.accessioned |
2023-01-09T11:58:17Z |
|
| dc.date.available |
2023-01-09T11:58:17Z |
|
| dc.identifier |
0b803046-80c7-456b-984f-615755528022 |
|
| dc.identifier |
10.1038/s41467-017-01103-4 |
|
| dc.identifier |
https://avesis.sdu.edu.tr/publication/details/0b803046-80c7-456b-984f-615755528022/oai |
|
| dc.identifier.uri |
http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/97536 |
|
| dc.description |
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. |
|
| dc.language |
eng |
|
| dc.rights |
info:eu-repo/semantics/closedAccess |
|
| dc.title |
A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover |
|
| dc.type |
info:eu-repo/semantics/article |
|