9t4t
Structure of Centrosomin (Cnn) partial PReM domain 490-579 WT of Drosophila melanogaster
Structural highlights
FunctionCNN_DROME Core component of the centrosome throughout spermatogenesis. May participate in mitotic spindle assembly and the mechanics of morphogenesis through an interaction with microtubules, either directly or indirectly. Is a target of several homeotic genes.[1] [2] Publication Abstract from PubMedMitotic centrosome maturation requires Polo/PLK1-dependent expansion of the pericentriolar material (PCM). In Drosophila, Centrosomin (Cnn) assembles a scaffold around mitotic centrioles through interactions between its PReM and CM2 domains. Here, we show that PReM adopts an autoinhibited helical hairpin conformation that prevents CM2 binding. Polo/PLK1 phosphorylation relieves this autoinhibition, enabling scaffold assembly, whereas phospho-blocking mutations disrupt PReM-CM2 binding in vitro and Cnn scaffold assembly in vivo. Potential functionally analogous domains have been identified in the human and C. elegans Cnn homologues CDK5RAP2 and SPD-5. We find that the human protein appears to share a structurally similar mechanism for scaffold assembly, but the worm protein does not. Consistent with this, deletion of these domains alters the dynamics of Cnn condensates in vitro, but has little effect on SPD-5 condensate dynamics. We conclude that Polo/PLK1 promotes mitotic centrosome assembly, at least in part, by relieving autoinhibitory intramolecular interactions. Polo/PLK1 phosphorylation relieves Centrosomin/Cnn autoinhibition to promote centrosome scaffold assembly.,Mohamad N, Wong SS, Majumdar A, Wainman A, Holland-Kaye I, Hubatsch L, Novak Z, Pozniakovsky A, Ruer-Gruss M, Haensele AFM, Caballe A, Johnson S, Lea SM, Hyman AA, Raff JW EMBO J. 2026 Sep;45(17):6320-6356. doi: 10.1038/s44318-026-00878-x. Epub 2026 Jul , 30. PMID:42533085[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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