9FH8

Crystal structure of the SPD-2 domain of Apis dorsata CEP192

Summary for 9FH8

• Entry DOI: 10.2210/pdb9fh8/pdb
• Descriptor: Centrosomal protein 192 (CEP192) (1 entity in total)
• Functional Keywords: centrosome, pcm, cell cycle
• Biological source: Apis dorsata (giant honeybee)
• Total number of polymer chains: 8
• Total formula weight: 309496.06

Authors

van Breugel, M. (deposition date: 2024-05-26, release date: 2025-03-26, Last modification date: 2025-04-02)

Primary citation

Hu, L.,Wainman, A.,Andreeva, A.,Apizi, M.,Alvarez-Rodrigo, I.,Wong, S.S.,Saurya, S.,Sheppard, D.,Cottee, M.,Johnson, S.,Lea, S.M.,Raff, J.W.,van Breugel, M.,Feng, Z.
The conserved Spd-2/CEP192 domain adopts a unique protein fold to promote centrosome scaffold assembly.
Sci Adv, 11:eadr5744-eadr5744, 2025

PubMed 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 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 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.

PubMed: 40106572
DOI: 10.1126/sciadv.adr5744

Experimental method

X-RAY DIFFRACTION (3.5 Å)