Cooperative unfolding of compact conformations of the intrinsically disordered protein osteopontin

Biochemistry. 2013 Aug 6;52(31):5167-75. doi: 10.1021/bi400502c. Epub 2013 Jul 24.

Abstract

Intrinsically disordered proteins (IDPs) constitute a class of biologically active proteins that lack defined tertiary and often secondary structure. The IDP Osteopontin (OPN), a cytokine involved in metastasis of several types of cancer, is shown to simultaneously sample extended, random coil-like conformations and stable, cooperatively folded conformations. By a combination of two magnetic resonance methods, electron paramagnetic resonance and nuclear magnetic resonance spectroscopy, we demonstrate that the OPN ensemble exhibits not only characteristics of an extended and flexible polypeptide, as expected for an IDP, but also simultaneously those of globular proteins, in particular sigmoidal structural denaturation profiles. Both types of states, extended and cooperatively folded, are populated simultaneously by OPN in its apo state. The heterogeneity of the structural properties of IDPs is thus shown to even involve cooperative folding and unfolding events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avian Proteins / chemistry*
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Intrinsically Disordered Proteins / chemistry
  • Intrinsically Disordered Proteins / genetics
  • Intrinsically Disordered Proteins / metabolism
  • Kinetics
  • Nuclear Magnetic Resonance, Biomolecular
  • Osteopontin / chemistry*
  • Osteopontin / genetics
  • Osteopontin / metabolism
  • Protein Conformation
  • Protein Folding
  • Protein Unfolding
  • Quail* / genetics
  • Quail* / metabolism

Substances

  • Avian Proteins
  • Intrinsically Disordered Proteins
  • Osteopontin