Roco Proteins: GTPases with a Baroque Structure and Mechanism
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, cilt.20, sa.1, 2019 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Derleme
- Cilt numarası: 20 Sayı: 1
- Basım Tarihi: 2019
- Doi Numarası: 10.3390/ijms20010147
- Dergi Adı: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Anahtar Kelimeler: Parkinson's disease, leucine-rich repeat kinase 2, Roco proteins, unconventional G-protein, GTPase mechanism, LEUCINE-RICH-REPEAT, ENVIRONMENTAL RISK-FACTORS, PARKINSONS-DISEASE, GTP-BINDING, LRRK2 GTPASE, DAP-KINASE, LEUCINE-RICH-REPEAT-KINASE-2 LRRK2, SIGNAL-TRANSDUCTION, GENE LRRK2, G-DOMAIN
- Süleyman Demirel Üniversitesi Adresli: Hayır
Özet
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.