5oi7 | pdb_00005oi7
Human CEP85 - coiled coil domain 4
Structural highlights
Function[CEP85_HUMAN] Acts as a negative regulator of NEK2 to maintain the centrosome integrity in interphase. Suppresses centrosome disjunction by inhibiting NEK2 kinase activity (PubMed:26220856).[1] Publication Abstract from PubMedCentrosomes are required for faithful chromosome segregation during mitosis. They are composed of a centriole pair that recruits and organizes the microtubule-nucleating pericentriolar material. Centriole duplication is tightly controlled in vivo and aberrations in this process are associated with several human diseases, including cancer and microcephaly. Although factors essential for centriole assembly, such as STIL and PLK4, have been identified, the underlying molecular mechanisms that drive this process are incompletely understood. Combining protein proximity mapping with high-resolution structural methods, we identify CEP85 as a centriole duplication factor that directly interacts with STIL through a highly conserved interaction interface involving a previously uncharacterised domain of STIL. Structure-guided mutational analyses in vivo demonstrate that this interaction is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly. Taken together, our results illuminate a molecular mechanism underpinning the spatiotemporal regulation of the early stages of centriole duplication. Direct binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly.,Liu Y, Gupta GD, Barnabas DD, Agircan FG, Mehmood S, Wu D, Coyaud E, Johnson CM, McLaughlin SH, Andreeva A, Freund SMV, Robinson CV, Cheung SWT, Raught B, Pelletier L, van Breugel M Nat Commun. 2018 Apr 30;9(1):1731. doi: 10.1038/s41467-018-04122-x. PMID:29712910[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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