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Bone recognition mechanism of porcine osteocalcin from crystal structure

Nature volume 425, pages 977–980 (2003)Cite this article

Abstract

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.

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Figure 1: Structure of pOC.
Figure 2: Model of pOC engaging an HA crystal based on a Ca2+ ion lattice match.

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Acknowledgements

We thank A. Viinberg for assistance with purification; M. Pereira and R. Ghirlando for help with sedimentation equilibrium data acquisition and data analysis, respectively; and W.-C. Hon for comments on the manuscript. Use of the IMCA-CAT beamline 17-ID at the Advanced Photon Source was supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Illinois Institute of Technology. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences. This work was supported by the Natural Sciences and Engineering Research Council (NSERC) of Canada.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Health Science, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada

    Quyen Q. Hoang & Daniel S. C. Yang

  2. Microstar Biotech Inc., 7 Innovation Drive, Flamborough, Ontario, L9H 7H9, Canada

    Quyen Q. Hoang

  3. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

    Frank Sicheri

  4. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

    Frank Sicheri

  5. Department of Biological, Chemical and Physical Sciences, Illinois Institute Technology, Chicago, Illinois, 60616, USA

    Andrew J. Howard

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Correspondence to Daniel S. C. Yang.

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Hoang, Q., Sicheri, F., Howard, A. et al. Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature 425, 977–980 (2003). https://doi.org/10.1038/nature02079

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