Commentary

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

Volume 3, Issue 2   April/May/June 2012
Pages 107 - 110
http://dx.doi.org/10.4161/sgtp.19380
Keywords: OCRL, Rab8, biosynthetic pathway, cilia, endocytosis
Authors: Nina Hagemann, Xiaomin Hou, Roger S. Goody, Aymelt Itzen and Kai S. Erdmann

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Abstract:
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.

Commentary to:
X Hou, N Hagemann, S Schoebel, W Blankenfeldt, RS Goody, KS Erdmann, A Itzen. A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1. EMBO J 2011; 30: 1659-70
PMID: 21378754

Received: October 31, 2011; Accepted: January 16, 2012

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