| dc.creator |
Versees, Wim |
|
| dc.creator |
Wauters, Lina |
|
| dc.creator |
Terheyden, Susanne |
|
| dc.creator |
Gilsbach, Bernd K. |
|
| dc.creator |
Leemans, Margaux |
|
| dc.creator |
Athanasopoulos, Panagiotis S. |
|
| dc.creator |
Guaitoli, Giambattista |
|
| dc.creator |
Wittinghofer, Alfred |
|
| dc.creator |
Gloeckner, Christian Johannes |
|
| dc.creator |
Kortholt, Arjan |
|
| dc.date |
2018-12-01T00:00:00Z |
|
| dc.date.accessioned |
2023-01-09T12:04:52Z |
|
| dc.date.available |
2023-01-09T12:04:52Z |
|
| dc.identifier |
83545413-fdb8-4583-ace0-ad0e72e16169 |
|
| dc.identifier |
10.1515/hsz-2018-0227 |
|
| dc.identifier |
https://avesis.sdu.edu.tr/publication/details/83545413-fdb8-4583-ace0-ad0e72e16169/oai |
|
| dc.identifier.uri |
http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/98072 |
|
| dc.description |
Roco proteins have come into focus after mutations in the gene coding for the human Roco protein Leucine-rich repeat kinase 2 ( LRRK2) were discovered to be one of the most common genetic causes of late onset Parkinson's disease. Roco proteins are characterized by a Roc domain responsible for GTP binding and hydrolysis, followed by a COR dimerization device. The regulation and function of this RocCOR domain tandem is still not completely understood. To fully biochemically characterize Roco proteins, we performed a systematic survey of the kinetic properties of several Roco protein family members, including LRRK2. Together, our results show that Roco proteins have a unique G-protein cycle. Our results confirm that Roco proteins have a low nucleotide affinity in the micromolar range and thus do not strictly depend on G-nucleotide exchange factors. Measurement of multiple and single turnover reactions shows that neither P-1 nor GDP release are rate-limiting, while this is the case for the GAP-mediated GTPase reaction of some small G-proteins like Ras and for most other high affinity Ras-like proteins, respectively. The K-M values of the reactions are in the range of the physiological GTP concentration, suggesting that LRRK2 functioning might be regulated by the cellular GTP level. |
|
| dc.language |
eng |
|
| dc.rights |
info:eu-repo/semantics/closedAccess |
|
| dc.title |
Biochemical and kinetic properties of the complex Roco G-protein cycle |
|
| dc.type |
info:eu-repo/semantics/article |
|