Skip NavigationSkip to Content
Return Return to Search Results

The conserved Spd-2/CEP192 domain adopts a unique protein fold to promote centrosome scaffold assembly

  1. Author:
    Hu, Liuyi [ORCID]
    Wainman, Alan [ORCID]
    Andreeva, Antonina [ORCID]
    Apizi, Muladili [ORCID]
    Alvarez-Rodrigo, Ines [ORCID]
    Wong, Siu-Shing [ORCID]
    Saurya, Saroj [ORCID]
    Sheppard, Devon [ORCID]
    Cottee, Matthew [ORCID]
    Johnson,Steven [ORCID]
    Lea,Susan [ORCID]
    Raff, Jordan W [ORCID]
    van Breugel, Mark [ORCID]
    Feng, Zhe [ORCID]

  2. Author Address

    State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China., Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK., Medical Research Council-Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK., Francis Crick Institute, London NW1 1AT, UK., Center for Structural Biology, CC R, NCI, Frederick, MD 21702-1201, USA.,
    1. Year: 2025
    2. Date: Mar 21
    3. Epub Date: 2025 03 19
  2. Journal: Science Advances
    1. 11
    2. 12
    3. Pages: eadr5744
  4. Type of Article: Article
  5. Article Number: eadr5744
  1. Abstract:

    Centrosomes form when centrioles assemble pericentriolar material (PCM) around themselves. Spd-2/CEP192 proteins, defined by a conserved "Spd-2 domain" (SP2D) comprising two closely spaced AspM-Spd-2-Hydin (ASH) domains, play a critical role in centrosome assembly. Here, we show that the SP2D does not target Drosophila Spd-2 to centrosomes but rather promotes PCM scaffold assembly. Crystal structures of the human and honeybee SP2D reveal an unusual "extended cradle" structure mediated by a conserved interaction interface between the two ASH domains. Mutations predicted to perturb this interface, including a human mutation associated with male infertility and Mosaic Variegated Aneuploidy, disrupt PCM scaffold assembly in flies. The SP2D is monomeric in solution, but the Drosophila SP2D can form higher-order oligomers upon phosphorylation by PLK1 (Polo-like kinase 1). Crystal-packing interactions and AlphaFold predictions suggest how SP2Ds might self-assemble, and mutations associated with one such potential dimerization interface markedly perturb SP2D oligomerization in vitro and PCM scaffold assembly in vivo.

    See More

External Sources

  1. View Full Text
  2. DOI: 10.1126/sciadv.adr5744
  3. PMID: 40106572
  4. PMCID: PMC11922060

Library Notes

  1. Fiscal Year: FY2024-2025
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel