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Biophys J. 2017 Apr 25;112(8):1586-1596. doi: 10.1016/j.bpj.2017.03.005.

Effect of Phosphorylation on a Human-like Osteopontin Peptide.

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Environment, Physical Sciences and Applied Mathematics (EPSAM), Keele University, Staffordshire, United Kingdom; Institut Laue-Langevin, Grenoble, France; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
Institut Laue-Langevin, Grenoble, France; Institut für Angewandte Physik, University of Tübingen, Tübingen, Germany.
Institut Laue-Langevin, Grenoble, France; Department of Chemistry, Division of Physical Chemistry, Lund University, Lund, Sweden.
Institut für Angewandte Physik, University of Tübingen, Tübingen, Germany.
Department of Chemistry, Division of Physical Chemistry, Lund University, Lund, Sweden.
Hannah Research Institute, Ayr, Scotland, United Kingdom.
Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, United Kingdom.
Institut Laue-Langevin, Grenoble, France.
ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, United Kingdom.
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware; The NIST Centre for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland. Electronic address:


The last decade established that the dynamic properties of the phosphoproteome are central to function and its modulation. The temporal dimension of phosphorylation effects remains nonetheless poorly understood, particularly for intrinsically disordered proteins. Osteopontin, selected for this study due to its key role in biomineralization, is expressed in many species and tissues to play a range of distinct roles. A notable property of highly phosphorylated isoforms of osteopontin is their ability to sequester nanoclusters of calcium phosphate to form a core-shell structure, in a fluid that is supersaturated but stable. In Biology, this process enables soft and hard tissues to coexist in the same organism with relative ease. Here, we extend our understanding of the effect of phosphorylation on a disordered protein, the recombinant human-like osteopontin rOPN. The solution structures of the phosphorylated and unphosphorylated rOPN were investigated by small-angle x-ray scattering and no significant changes were detected on the radius of gyration or maximum interatomic distance. The picosecond-to-nanosecond dynamics of the hydrated powders of the two rOPN forms were further compared by elastic and quasi-elastic incoherent neutron scattering. Phosphorylation was found to block some nanosecond side-chain motions while increasing the flexibility of other side chains on the faster timescale. Phosphorylation can thus selectively change the dynamic behavior of even a highly disordered protein such as osteopontin. Through such an effect on rOPN, phosphorylation can direct allosteric mechanisms, interactions with substrates, cofactors and, in this case, amorphous or crystalline biominerals.

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