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.
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December 2016
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Views of the Fc region of human immunoglobulin A (IgA) with interaction sites for key host receptors highlighted in the upper images, and those for bacterial IgA binding proteins in the lower ones. The remarkable co-localisation of these sites illustrates how various bacterial pathogens have co-opted sites on immunoglobulins as an effective means to block the elimination mechanisms which immunoglobulins normally trigger. See pp. 1651–1658 for further information. Image provided by J. Woof.
Review Article|
December 02 2016
The unconventional G-protein cycle of LRRK2 and Roco proteins
Susanne Terheyden;
Susanne Terheyden
Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands
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Laura M. Nederveen-Schippers;
Laura M. Nederveen-Schippers
Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands
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Arjan Kortholt
Arjan Kortholt
Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands
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Publisher: Portland Press Ltd
Received:
August 03 2016
Revision Received:
September 09 2016
Accepted:
September 16 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem Soc Trans (2016) 44 (6): 1611–1616.
Article history
Received:
August 03 2016
Revision Received:
September 09 2016
Accepted:
September 16 2016
Citation
Susanne Terheyden, Laura M. Nederveen-Schippers, Arjan Kortholt; The unconventional G-protein cycle of LRRK2 and Roco proteins. Biochem Soc Trans 15 December 2016; 44 (6): 1611–1616. doi: https://doi.org/10.1042/BST20160224
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