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The Ciliopathy-Associated Cep104 Protein Interacts with Tubulin and Nek1 Kinase

DOI: 10.1016/j.str.2016.11.014 DOI Help

Authors: Caezar Al-jassar (MRC Laboratory of Molecular Biology) , Antonina Andreeva (MRC Laboratory of Molecular Biology) , Deepak D. Barnabas (MRC Laboratory of Molecular Biology) , Stephen H. Mclaughlin (MRC Laboratory of Molecular Biology) , Christopher M. Johnson (MRC Laboratory of Molecular Biology) , Minmin Yu (MRC Laboratory of Molecular Biology) , Mark Van Breugel (MRC Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure

State: Published (Approved)
Published: December 2016
Diamond Proposal Number(s): 11235

Open Access Open Access

Abstract: Cilia are thin cell projections with essential roles in cell motility, fluid movement, sensing, and signaling. They are templated from centrioles that dock against the plasma membrane and subsequently extend their peripheral microtubule array. The molecular mechanisms underpinning cilia assembly are incompletely understood. Cep104 is a key factor involved in cilia formation and length regulation that rides on the ends of elongating and shrinking cilia. It is mutated in Joubert syndrome, a genetically heterogeneous ciliopathy. Here we provide structural and biochemical data that Cep104 contains a tubulin-binding TOG (tumor overexpressed gene) domain and a novel C2HC zinc finger array. Furthermore, we identify the kinase Nek1, another ciliopathy-associated protein, as a potential binding partner of this array. Finally, we show that Nek1 competes for binding to Cep104 with the distal centriole-capping protein CP110. Our data suggest a model for Cep104 activity during ciliogenesis and provide a novel link between Cep104 and Nek1.

Journal Keywords: Cep104; TOG; tubulin; zinc finger; Nek1; CP110; centriole; basal body; cilia

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Other Facilities: European Synchrotron Radiation Facility

Documents:
1-s2.0-S0969212616303562-main.pdf