Roco Proteins: GTPases with a Baroque Structure and Mechanism.

TitleRoco Proteins: GTPases with a Baroque Structure and Mechanism.
Publication TypeJournal Article
Year of Publication2019
AuthorsWauters, L., W. Versées, and A. Kortholt
JournalInt J Mol Sci
Date Published2019 Jan 03
KeywordsAnimals, Dictyostelium, Evolution, Molecular, GTP Phosphohydrolases, GTP-Binding Proteins, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Parkinson Disease, Protein Domains, Protein Structure, Tertiary

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.

Alternate JournalInt J Mol Sci
PubMed ID30609797
PubMed Central IDPMC6337361
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