9C72
Structure of the ASH3 domain of Drosophila melanogaster Spd-2
Summary for 9C72
| Entry DOI | 10.2210/pdb9c72/pdb |
| Descriptor | Spindle defective 2, SULFATE ION, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | centrosome, pericentriolar material, drosophila, cytosolic protein |
| Biological source | Drosophila melanogaster (fruit fly) |
| Total number of polymer chains | 1 |
| Total formula weight | 13674.45 |
| Authors | |
| 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 Cited by 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: 40106572DOI: 10.1126/sciadv.adr5744 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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