PDBsum entry 6ewh

Cytosolic protein

PDB id: 6ewh

Contents

Protein chain

181 a.a.

Waters ×202

PDB id:

6ewh

Name:

Cytosolic protein

Title:

Oreochromis niloticus cep120 second c2 domain (c2b) g307s mutant

Structure:

Centrosomal protein 120. Chain: a. Engineered: yes

Source:

Oreochromis niloticus. Nile tilapia. Organism_taxid: 8128. Gene: cep120. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.50Å R-factor: 0.185 R-free: 0.206

Authors:

M.Van Breugel,C.Al-Jassar,M.Yu

Key ref:

N.Joseph et al. (2018). Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis. Cell Rep, 23, 2805-2818. PubMed id: 29847808

Date:

04-Nov-17 Release date: 02-May-18

Protein chain

I3K8D3  (I3K8D3_ORENI) -  Centrosomal protein 120 from Oreochromis niloticus

Seq: 995 a.a.

Struc: 181 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

Cell Rep 23:2805-2818 (2018)

PubMed id: 29847808

Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis.

N.Joseph, C.Al-Jassar, C.M.Johnson, A.Andreeva, D.D.Barnabas, S.M.V.Freund, F.Gergely, M.van Breugel.

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.