Roco Proteins: GTPases with a Baroque Structure and Mechanism

Lina Wauters, Wim Versées, Arjan Kortholt

Research output: Contribution to journalScientific review

14 Citations (Scopus)
9 Downloads (Pure)


Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of genetically inherited Parkinson's Disease (PD). LRRK2 is a large, multi-domain protein belonging to the Roco protein family, a family of GTPases characterized by a central RocCOR (Ras of complex proteins/C-terminal of Roc) domain tandem. Despite the progress in characterizing the GTPase function of Roco proteins, there is still an ongoing debate concerning the working mechanism of Roco proteins in general, and LRRK2 in particular. This review consists of two parts. First, an overview is given of the wide evolutionary range of Roco proteins, leading to a variety of physiological functions. The second part focusses on the GTPase function of the RocCOR domain tandem central to the action of all Roco proteins, and progress in the understanding of its structure and biochemistry is discussed and reviewed. Finally, based on the recent work of our and other labs, a new working hypothesis for the mechanism of Roco proteins is proposed.

Original languageEnglish
Article number147
Number of pages21
JournalInternational Journal of Molecular Sciences
Issue number1
Publication statusPublished - 3 Jan 2019


  • GTPase mechanism
  • Leucine-rich repeat kinase 2
  • Parkinson’s disease
  • Roco proteins
  • Unconventional G-protein


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