CFAP410 has a bimodular architecture with a conserved surface patch on its N-terminal leucine-rich repeat motif for binding interaction partners

Cilia and flagella associated protein 410 (CFAP410) is a protein localized at the basal body of cilia/flagella and plays essential roles in ciliogenesis. Multiple single amino acid mutations in CFAP410 have been identified in patients. However, the molecular mechanism for how the mutations cause these disorders remains poorly understood due to a lack of high-resolution structures of the protein. Our studies demonstrate that CFAP410 adopts a bimodular architecture. We have previously reported our structural studies on the C-terminal domain (CTD) of CFAP410 from various organisms. Here we report a 1.0-Å resolution crystal structure of the N-terminal domain (NTD) of <i>Trypanosoma brucei</i> CFAP410. We further examined how the disease-causing mutations in this domain may affect the folding and structural stability of CFAP410. Our results suggest that the single-residue mutations in the CFAP410-NTD cause human diseases by destabilizing the structure that subsequently disrupts its interaction with other partners.

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Publication Details

Journal
Frontiers in Cell and Developmental Biology
Published
2025-02-13
DOI
https://doi.org/10.3389/fcell.2025.1507470
Primary Topic
Chromosomal and Genetic Variations
Type
article
Field-Weighted Citation Impact
0.00

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article

CFAP410 has a bimodular architecture with a conserved surface patch on its N-terminal leucine-rich repeat motif for binding interaction partners

Laryssa Vanessa de Liz, Alexander Stadler, Xuan Deng, Kaiyao Huang et al.
1 links
Frontiers in Cell and Developmental Biology
Chromosomal and Genetic Variations
article

CFAP410 has a bimodular architecture with a conserved surface patch on its N-terminal leucine-rich repeat motif for binding interaction partners

Laryssa Vanessa de Liz, Alexander Stadler, Xuan Deng, Kaiyao Huang, Gang Dong, Jack Daniel Sunter, Robbie Crickley, Barbora Mikolaskova, Katharina Korbula, Heloisa B. Gabriel, Sue Vaughan, Bojan Žagrović, Santiago Alonso-Gil
article en

Abstract

Cilia and flagella associated protein 410 (CFAP410) is a protein localized at the basal body of cilia/flagella and plays essential roles in ciliogenesis. Multiple single amino acid mutations in CFAP410 have been identified in patients. However, the molecular mechanism for how the mutations cause these disorders remains poorly understood due to a lack of high-resolution structures of the protein. Our studies demonstrate that CFAP410 adopts a bimodular architecture. We have previously reported our structural studies on the C-terminal domain (CTD) of CFAP410 from various organisms. Here we report a 1.0-Å resolution crystal structure of the N-terminal domain (NTD) of <i>Trypanosoma brucei</i> CFAP410. We further examined how the disease-causing mutations in this domain may affect the folding and structural stability of CFAP410. Our results suggest that the single-residue mutations in the CFAP410-NTD cause human diseases by destabilizing the structure that subsequently disrupts its interaction with other partners.

Frontiers in Cell and Developmental BiologyVol. 13
Oxford Brookes University (GB), University of Vienna (AT), Chinese Academy of Sciences (CN), Max Perutz Labs (AT), Institute of Hydrobiology (CN), Vienna Biocenter (AT), Medical University of Vienna (AT)
Oxford Brookes University, Wellcome Trust, European Commission, European Synchrotron Radiation Facility, Austrian Science Fund
Openalex Percentile: Top 98%
Chromosomal and Genetic Variations
DOIOpen Access PDFOpenAlex
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