The unconventional G-protein cycle of LRRK2 and Roco proteins

Susanne Terheyden, Laura M Nederveen-Schippers, Arjan Kortholt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1611-1616
Number of pages6
JournalBiochemical Society Transactions
Volume44
Issue number6
DOIs
Publication statusPublished - 15-Dec-2016

Keywords

  • REPEAT KINASE 2
  • DISEASE-ASSOCIATED MUTATIONS
  • FAMILIAL PARKINSONS-DISEASE
  • GTP-BINDING
  • NEURONAL TOXICITY
  • DOMAIN
  • MUTANT
  • LEUCINE-RICH-REPEAT-KINASE-2
  • HYDROLYSIS
  • REVEALS

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