Bone recognition mechanism of porcine osteocalcin from crystal structure

Osteocalcin is the most abundant noncollagenous protein in bone1, and its concentration in serum is closely linked to bone metabolism and serves as a biological marker for the clinical assessment of bone disease2. Although its precise mechanism of action is unclear, osteocalcin influences bone mineralization3,4, in part through its ability to bind with high affinity to the mineral component of bone, hydroxyapatite5. In addition to binding to hydroxyapatite, osteocalcin functions in cell signalling and the recruitment of osteoclasts6 and osteoblasts7, which have active roles in bone resorption and deposition, respectively. Here we present the X-ray crystal structure of porcine osteocalcin at 2.0 Å 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.