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Publication Abstract from PubMed

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.

The conserved Spd-2/CEP192 domain adopts a unique protein fold to promote centrosome scaffold assembly.,Hu L, Wainman A, Andreeva A, Apizi M, Alvarez-Rodrigo I, Wong SS, Saurya S, Sheppard D, Cottee M, Johnson S, Lea SM, Raff JW, van Breugel M, Feng Z Sci Adv. 2025 Mar 21;11(12):eadr5744. doi: 10.1126/sciadv.adr5744. Epub 2025 Mar , 19. PMID:40106572^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.