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.
- MeSH
- ciliopatie genetika MeSH
- cirkulární dichroismus MeSH
- HEK293 buňky MeSH
- konformace proteinů MeSH
- lidé MeSH
- mikrotubulární proteiny chemie genetika metabolismus MeSH
- molekulární modely MeSH
- mutace * MeSH
- protein-serin-threoninkinasy chemie metabolismus MeSH
- proteinové domény MeSH
- proteiny asociované s mikrotubuly metabolismus MeSH
- stabilita proteinů MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- mikrotubulární proteiny analýza chemie imunologie MeSH
- monoklonální protilátky biosyntéza diagnostické užití normy MeSH
- mozek cytologie fyziologie MeSH
- neurony cytologie fyziologie MeSH
- registrace MeSH
- senzitivita a specificita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
