The unconventional G-protein cycle of LRRK2 and Roco proteins
BIOCHEMICAL SOCIETY TRANSACTIONS, vol.44, pp.1611-1616, 2016 (SCI-Expanded, Scopus)
- Publication Type: Article / Review
- Volume: 44
- Publication Date: 2016
- Doi Number: 10.1042/bst20160224
- Journal Name: BIOCHEMICAL SOCIETY TRANSACTIONS
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.1611-1616
- Open Archive Collection: AVESIS Open Access Collection
- Süleyman Demirel University Affiliated: No
Abstract
Mutations in the human leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of hereditary Parkinson's disease (PD). LRRK2 belongs to the Roco family of proteins, which are characterized by the presence of a Ras of complex proteins domain (Roc), a C-terminal of Roc domain (COR) and a kinase domain. Despite intensive research, much remains unknown about activity and the effect of PD-associated mutations. Recent biochemical and structural studies suggest that LRRK2 and Roco proteins are noncanonical G-proteins that do not depend on guanine nucleotide exchange factors or GTPase-activating proteins for activation. In this review, we will discuss the unusual G-protein cycle of LRRK2 in the context of the complex intramolecular LRRK2 activation mechanism.