P005
Analysis of LRRK2 repeat domains: length, number and
boundaries and possible protein interaction surfaces
Ryan D Mills1, Terrence Damian Mulhern2, Heung-Chin
Cheng1 and Janetta G. Culvenor1
1
University of Melbourne, Parkville, Australia
2
University of Melbourne, MELBOURNE, Australia
The leucine-rich repeat kinase two protein (LRRK2) is a large
complex multi-domain protein with two enzymatic domains and
four predicted repeat regions. While genetic research on LRRK2
is now extensive, and many studies have been published for
cellular and animal models, there is still a lack of literature considering LRRK2 from a biochemical and structural viewpoint.
Utilizing bioinformatic tools and sequence analysis we have
predicted the repeat length, number and boundaries for the
armadillo, ankyrin, leucine-rich repeat, and WD40 repeat regions.
Key sites of Parkinsonism associated mutations were located and
the likely effect on structure is considered. Possible ligand interacting residues were also identified within the repeat domains.
The detailed analysis is presented with reference to experimental data for LRRK2 and other well characterized repeat domain
proteins.
Acknowledgements:
We thank the Australian Brain Foundation and the Australian
National Health and Medical Research Council for financial
support. Ryan Mills was supported by an Australian Postgraduate
Research Award, a Dowd Neuroscience fellowship, and an
Australian Institute of Nuclear Science and Engineering award.