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Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies

DOI: 10.1016/j.str.2021.08.007 DOI Help

Authors: Ivan Rosa E Silva (Queen Mary University of London; Medical Research Council – Laboratory of Molecular Biology) , Lucia Binó (Masaryk University) , Christopher M. Johnson (Medical Research Council – Laboratory of Molecular Biology) , Trevor J. Rutherford (Medical Research Council – Laboratory of Molecular Biology) , David Neuhaus (Medical Research Council – Laboratory of Molecular Biology) , Antonina Andreeva (Medical Research Council – Laboratory of Molecular Biology) , Lukáš Čajánek (Masaryk University) , Mark Van Breugel (Queen Mary University of London; Medical Research Council – Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Structure , VOL 68

State: Published (Approved)
Published: September 2021
Diamond Proposal Number(s): 15916 , 21426

Open Access Open Access

Abstract: Cilia formation is essential for human life. One of the earliest events in the ciliogenesis program is the recruitment of tau-tubulin kinase 2 (TTBK2) by the centriole distal appendage component CEP164. Due to the lack of high-resolution structural information on this complex, it is unclear how it is affected in human ciliopathies such as nephronophthisis. Furthermore, it is poorly understood if binding to CEP164 influences TTBK2 activities. Here, we present a detailed biochemical, structural, and functional analysis of the CEP164-TTBK2 complex and demonstrate how it is compromised by two ciliopathic mutations in CEP164. Moreover, we also provide insights into how binding to CEP164 is coordinated with TTBK2 activities. Together, our data deepen our understanding of a crucial step in cilia formation and will inform future studies aimed at restoring CEP164 functionality in a debilitating human ciliopathy.

Journal Keywords: CEP164; TTBK2; cilia; ciliogenesis; ciliopathy; nephronophthisis; basal body; centriole; distal appendage; centrosome

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 18/09/2021 11:59

Documents:
1-s2.0-S0969212621003026-main.pdf

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)