핵심 개념
The author demonstrates that the tetrameric assembly of CFAP410's C-terminal domain is crucial for its correct localization to the basal body, shedding light on how mutations like L224P can lead to ciliopathies.
초록
The study focuses on CFAP410, a protein essential for ciliogenesis and associated with various disorders. Structural analysis reveals a tetrameric helical bundle in the C-terminal domain crucial for proper localization to the basal body. Mutations disrupting this assembly, like L224P, can result in severe conditions such as spondylometaphyseal dysplasia. In vivo experiments in Trypanosoma brucei confirm the importance of this tetrameric structure for proper function and localization of CFAP410. The findings provide insights into the molecular mechanisms underlying ciliopathies and highlight the significance of protein structure in cellular processes.
통계
Homo sapiens CFAP410 consists of 255 amino acids.
Mutations identified in patients include I35F, C61Y, R73P, Y107C, Y107H, V111M, and L224P.
Crystal structures reveal a tetrameric helical bundle formation in CFAP410's C-terminal domain.
The L224P mutation disrupts tetramer assembly and abolishes basal body localization.
TbCFAP410 depletion leads to cytokinesis defects in T. brucei.
인용구
"The tightly packed eight-helix bundle of the CTD controls the specific localization of CFAP410 to the basal body possibly by directly interacting with NEK1."
"Depletion of TbCFAP410 after RNAi resulted in aberrant cells with multiple kinetoplasts and nuclei appearing."
"The disrupted location of TbCFAP410-L272P to the basal body could be attributed to its abolished interaction with NEK1."