6ewp
From Proteopedia
Mus musculus CEP120 third C2 domain (C2C)
Structural highlights
FunctionCE120_MOUSE Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis.[1] [2] [3] Publication Abstract from PubMedCiliopathies are a group of genetic disorders caused by a failure to form functional cilia. Due to a lack of structural information, it is currently poorly understood how ciliopathic mutations affect protein functionality to give rise to the underlying disease. Using X-ray crystallography, we show that the ciliopathy-associated centriolar protein CEP120 contains three C2 domains. The point mutations V194A and A199P, which cause Joubert syndrome (JS) and Jeune asphyxiating thoracic dystrophy (JATD), respectively, both reduce the thermostability of the second C2 domain by targeting residues that point toward its hydrophobic core. Genome-engineered cells homozygous for these mutations have largely normal centriole numbers but show reduced CEP120 levels, compromised recruitment of distal centriole markers, and deficient cilia formation. Our results provide insight into the disease mechanism of two ciliopathic mutations in CEP120, identify putative binding partners of CEP120 C2B, and suggest a complex genotype-phenotype relation of the CEP120 ciliopathy alleles. Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis.,Joseph N, Al-Jassar C, Johnson CM, Andreeva A, Barnabas DD, Freund SMV, Gergely F, van Breugel M Cell Rep. 2018 May 29;23(9):2805-2818. doi: 10.1016/j.celrep.2018.04.100. PMID:29847808[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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