Dynamic footprint of sequestration in the molecular fluctuations of osteopontin

Lenton, S., Seydel, T., Nylander, T., Holt, C. , Härtlein, M., Teixeira, S. and Zaccai, G. (2015) Dynamic footprint of sequestration in the molecular fluctuations of osteopontin. Journal of the Royal Society: Interface, 12(110), 20150506. (doi: 10.1098/rsif.2015.0506) (PMID:26354827)

Abstract

The sequestration of calcium phosphate by unfolded proteins is fundamental to the stabilization of biofluids supersaturated with respect to hydroxyapatite, such as milk, blood or urine. The unfolded state of osteopontin (OPN) is thought to be a prerequisite for this activity, which leads to the formation of core–shell calcium phosphate nanoclusters. We report on the structures and dynamics of a native OPN peptide from bovine milk, studied by neutron spectroscopy and small-angle X-ray and neutron scattering. The effects of sequestration are quantified on the nanosecond– ångström resolution by elastic incoherent neutron scattering. The molecular fluctuations of the free phosphopeptide are in agreement with a highly flexible protein. An increased resilience to diffusive motions of OPN is corroborated by molecular fluctuations similar to those observed for globular proteins, yet retaining conformational flexibilities. The results bring insight into the modulation of the activity of OPN and phosphopeptides with a role in the control of biomineralization. The quantification of such effects provides an important handle for the future design of new peptides based on the dynamics–activity relationship.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Holt, Dr Carl
• Authors: Lenton, S., Seydel, T., Nylander, T., Holt, C., Härtlein, M., Teixeira, S., and Zaccai, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Journal of the Royal Society: Interface
• Publisher: The Royal Society
• ISSN: 1742-5689
• ISSN (Online): 1742-5662