Structural and mutational analyses of decarboxylated osteocalcin provide insight into its adiponectin-inducing activity

Mineyuki Mizuguchi*, Takeshi Yokoyama, Takahito Otani, Shiori Kuribara, Yuko Nabeshima, Takayuki Obita, Masato Hirata, Keiichi Kawano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

An acidic environment in bone is essential for bone metabolism and the production of decarboxylated osteocalcin, which functions as a regulatory hormone of glucose metabolism. Here, we describe the high-resolution X-ray crystal structure of decarboxylated osteocalcin under acidic conditions. Decarboxylated osteocalcin at pH 2.0 retains the α-helix structure of native osteocalcin with three γ-carboxyglutamic acid residues at neutral pH. This implies that decarboxylated osteocalcin is stable under an acidic environment in bone. In addition, site-directed mutagenesis revealed that Glu17 and Glu21 are important for the adiponectin-inducing activity of decarboxylated osteocalcin. These findings suggest that the receptor of decarboxylated osteocalcin responds to the negative charge in helix 1 of osteocalcin.

Original languageEnglish
Pages (from-to)1479-1488
Number of pages10
JournalFEBS Letters
Volume597
Issue number11
DOIs
StatePublished - 2023/06

Keywords

  • GPRC6A
  • adiponectin
  • adiponectin-inducing activity
  • decarboxylated osteocalcin
  • glucose metabolism
  • helix

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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