6EWI

Oreochromis niloticus CEP120 second C2 domain (C2B) A200P + G307S mutant

Summary for 6EWI

• Entry DOI: 10.2210/pdb6ewi/pdb
• Descriptor: Centrosomal protein 120 (2 entities in total)
• Functional Keywords: centriole centrosome basal body cilia, cytosolic protein
• Biological source: Oreochromis niloticus (Nile tilapia)
• Total number of polymer chains: 2
• Total formula weight: 42101.98

Authors

van Breugel, M. (deposition date: 2017-11-04, release date: 2018-05-02, Last modification date: 2024-01-17)

Primary citation

Joseph, N.,Al-Jassar, C.,Johnson, C.M.,Andreeva, A.,Barnabas, D.D.,Freund, S.M.V.,Gergely, F.,van Breugel, M.
Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis.
Cell Rep, 23:2805-2818, 2018

PubMed Abstract: Ciliopathies 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.

PubMed: 29847808
DOI: 10.1016/j.celrep.2018.04.100

Experimental method

X-RAY DIFFRACTION (2.1 Å)