The unconventional G-protein cycle of LRRK2 and Roco proteins

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Terheyden S., Nederveen-Schippers L. M. , Kortholt A.

BIOCHEMICAL SOCIETY TRANSACTIONS, vol.44, pp.1611-1616, 2016 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 44
  • Publication Date: 2016
  • Doi Number: 10.1042/bst20160224
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.1611-1616


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.