Bone recognition mechanism of porcine osteocalcin from crystal structure

Nature. 2003 Oct 30;425(6961):977-80. doi: 10.1038/nature02079.

Abstract

Osteocalcin is the most abundant noncollagenous protein in bone, and its concentration in serum is closely linked to bone metabolism and serves as a biological marker for the clinical assessment of bone disease. Although its precise mechanism of action is unclear, osteocalcin influences bone mineralization, in part through its ability to bind with high affinity to the mineral component of bone, hydroxyapatite. In addition to binding to hydroxyapatite, osteocalcin functions in cell signalling and the recruitment of osteoclasts and osteoblasts, which have active roles in bone resorption and deposition, respectively. Here we present the X-ray crystal structure of porcine osteocalcin at 2.0 A resolution, which reveals a negatively charged protein surface that coordinates five calcium ions in a spatial orientation that is complementary to calcium ions in a hydroxyapatite crystal lattice. On the basis of our findings, we propose a model of osteocalcin binding to hydroxyapatite and draw parallels with other proteins that engage crystal lattices.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone and Bones / chemistry
  • Bone and Bones / metabolism*
  • Calcium / metabolism
  • Crystallization
  • Crystallography, X-Ray
  • Durapatite / metabolism
  • Models, Molecular
  • Osteocalcin / chemistry*
  • Osteocalcin / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Static Electricity
  • Structure-Activity Relationship
  • Substrate Specificity
  • Swine

Substances

  • Osteocalcin
  • Durapatite
  • Calcium

Associated data

  • PDB/1Q8H