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Roco Proteins and the Parkinson’s Disease-Associated LRRK2

1,2,* and 2,3,4,*
1
Department of Public Health, Wuhan University of Science and Technology School of Medicine, Wuhan 430081, China
2
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
4
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 4074; https://doi.org/10.3390/ijms19124074
Received: 15 November 2018 / Revised: 11 December 2018 / Accepted: 14 December 2018 / Published: 17 December 2018
(This article belongs to the Special Issue Small GTPases)
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PDF [1068 KB, uploaded 17 December 2018]
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Abstract

Small G-proteins are structurally-conserved modules that function as molecular on-off switches. They function in many different cellular processes with differential specificity determined by the unique effector-binding surfaces, which undergo conformational changes during the switching action. These switches are typically standalone monomeric modules that form transient heterodimers with specific effector proteins in the ‘on’ state, and cycle to back to the monomeric conformation in the ‘off’ state. A new class of small G-proteins called “Roco” was discovered about a decade ago; this class is distinct from the typical G-proteins in several intriguing ways. Their switch module resides within a polypeptide chain of a large multi-domain protein, always adjacent to a unique domain called COR, and its effector kinase often resides within the same polypeptide. As such, the mechanisms of action of the Roco G-proteins are likely to differ from those of the typical G-proteins. Understanding these mechanisms is important because aberrant activity in the human Roco protein LRRK2 is associated with the pathogenesis of Parkinson’s disease. This review provides an update on the current state of our understanding of the Roco G-proteins and the prospects of targeting them for therapeutic purposes. View Full-Text
Keywords: Roc; Intramolecular mechanism; Small GTPase; LRRK2 Roc; Intramolecular mechanism; Small GTPase; LRRK2
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Liao, J.; Hoang, Q.Q. Roco Proteins and the Parkinson’s Disease-Associated LRRK2. Int. J. Mol. Sci. 2018, 19, 4074.

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