Various investigators have identified the major domain organization of LRRK2 (leucine-rich repeat kinase 2), which includes a GTPase ROC (Ras of complex proteins) domain followed by a COR (C-terminal of ROC) domain and a protein kinase domain. In addition, there are four domains composed of structural repeat motifs likely to be involved in regulation and localization of this complex protein. In the present paper, we report our bioinformatic analyses of the human LRRK2 amino acid sequence to predict the repeat size, number and likely boundaries for the armadillo repeat, ankyrin repeat, the leucine-rich repeat and WD40 repeat regions of LRRK2. Homology modelling using known protein structures with similar domains was used to predict structures, exposed residues and location of mutations for these repeat regions. We predict that the armadillo repeats, ankyrin repeats and leucine-rich repeats together form an extended N-terminal flexible ‘solenoid’-like structure composed of tandem repeat modules likely to be important in anchoring to the membrane and cytoskeletal structures as well as binding to other protein ligands. Near the C-terminus of LRRK2, the WD40 repeat region is predicted to form a closed propeller structure that is important for protein complex formation.
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Conference Article|
September 19 2012
Analysis of LRRK2 accessory repeat domains: prediction of repeat length, number and sites of Parkinson's disease mutations
Ryan D. Mills;
Ryan D. Mills
*Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia
†Department of Pathology, University of Melbourne, Victoria 3010, Australia
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Terrence D. Mulhern;
Terrence D. Mulhern
*Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia
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Heung-Chin Cheng;
Heung-Chin Cheng
*Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia
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Janetta G. Culvenor
Janetta G. Culvenor
1
†Department of Pathology, University of Melbourne, Victoria 3010, Australia
1To whom correspondence should be addressed (emailj.culvenor@unimelb.edu.au).
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Publisher: Portland Press Ltd
Received:
March 26 2012
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (5): 1086–1089.
Article history
Received:
March 26 2012
Citation
Ryan D. Mills, Terrence D. Mulhern, Heung-Chin Cheng, Janetta G. Culvenor; Analysis of LRRK2 accessory repeat domains: prediction of repeat length, number and sites of Parkinson's disease mutations. Biochem Soc Trans 1 October 2012; 40 (5): 1086–1089. doi: https://doi.org/10.1042/BST20120088
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