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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cellular Biochemistry
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1507470
This article is part of the Research Topic Advances in Cilia and Flagella Research View all 3 articles

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

Provisionally accepted
Alexander Stadler Alexander Stadler 1Heloisa B Gabriel Heloisa B Gabriel 2Laryssa V De Liz Laryssa V De Liz 2Santiago Alonso-Gil Santiago Alonso-Gil 3Xuan Deng Xuan Deng 4Robbie Crickley Robbie Crickley 2Katharina Korbula Katharina Korbula 1Barbora Mikolaskova Barbora Mikolaskova 1Sue Vaughan Sue Vaughan 2Kaiyao Huang Kaiyao Huang 4Bojan Žagrović Bojan Žagrović 3Jack Sunter Jack Sunter 2Gang Dong Gang Dong 1*
  • 1 Center for Medical Biochemistry, Medical University of Vienna, Vienna, Austria
  • 2 Oxford Brookes University, Oxford, England, United Kingdom
  • 3 University of Vienna, Vienna, Vienna, Austria
  • 4 Institute of Hydrobiology, Chinese Academy of Sciences (CAS), Wuhan, Hubei Province, China

The final, formatted version of the article will be published soon.

    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 Trypanosoma brucei 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.

    Keywords: CFAP410, Cilium, ciliopathies, flagellum, protein, Structure

    Received: 07 Oct 2024; Accepted: 09 Jan 2025.

    Copyright: © 2025 Stadler, Gabriel, De Liz, Alonso-Gil, Deng, Crickley, Korbula, Mikolaskova, Vaughan, Huang, Žagrović, Sunter and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Gang Dong, Center for Medical Biochemistry, Medical University of Vienna, Vienna, 1030, Austria

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.