The conserved Spd-2/CEP192 domain adopts a unique protein fold to promote centrosome scaffold assembly.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40106572.
- Also identified by DOI 10.1126/sciadv.adr5744 and PMC identifier 11922060.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Drosophila</i> 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 <i>Drosophila</i> 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.
Medical subject headings
- Centrosome
- Drosophila Proteins
- Protein Folding
- Cell Cycle Proteins