Crystal structure of the Rab binding domain of OCRL1 in complex with Rab8 and functional implications of the OCRL1/Rab8 module for Lowe syndrome.

Nina Hagemann, Xiaomin Hou, Roger S Goody, Aymelt Itzen, Kai S Erdmann

Department of Biochemistry II, Ruhr-University Bochum, Bochum, Germany.

Small GTPases 2012 Apr-Jun

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Mutations of the inositol-5-phosphatase OCRL1 cause Lowe syndrome. Lowe syndrome is an inherited disease characterized by renal dysfunction and impaired development of the eye and the nervous system. OCRL1 is a Rab effector protein that can bind to a large number of different Rab proteins. We have recently determined the X-ray structure of the Rab-binding domain of OCRL1 in complex with Rab8. Furthermore, we have characterized point mutations that abolish binding to Rab proteins and cause Lowe syndrome. Here we shortly review our recent biophysical and structural work and discuss possible functional implications of our finding that Rab8 binds with the highest affinity to OCRL1 among the Rab proteins tested. This could direct further work on OCRL1 leading to a better understanding of the complex disease mechanism of Lowe syndrome.

Citation

Nina Hagemann, Xiaomin Hou, Roger S Goody, Aymelt Itzen, Kai S Erdmann. Crystal structure of the Rab binding domain of OCRL1 in complex with Rab8 and functional implications of the OCRL1/Rab8 module for Lowe syndrome. Small GTPases. 2012 Apr-Jun;3(2):107-10