Crystal structure of the Golgi casein kinase

Junyu Xiao, Vincent S. Tagliabracci, Jianzhong Wen, Soo A. Kim, Jack E. Dixon

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The family with sequence similarity 20 (Fam20) kinases phosphorylate extracellular substrates and play important roles in biomineralization. Fam20C is the Golgi casein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs. Mutations in Fam20C cause Raine syndrome, an osteosclerotic bone dysplasia. Here we report the crystal structure of the Fam20C ortholog from Caenorhabditis elegans. The nucleotide-free and Mn/ ADP-bound structures unveil an atypical protein kinase-like fold and highlight residues critical for activity. The position of the regulatory αC helix and the lack of an activation loop indicate an architecture primed for efficient catalysis. Furthermore, several distinct elements, including the presence of disulfide bonds, suggest that the Fam20 family diverged early in the evolution of the protein kinase superfamily. Our results reinforce the structural diversity of protein kinases and have important implications for patients with disorders of biomineralization.

Original languageEnglish (US)
Pages (from-to)10574-10579
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number26
DOIs
StatePublished - Jun 25 2013

Keywords

  • Amelogenesis imperfecta
  • Enamel renal syndrome
  • Fam20A
  • Fam20B
  • Hypophosphatemia

ASJC Scopus subject areas

  • General

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