Urea promotes polyproline II helix formation: implications for protein denatured states

Biochemistry. 2005 Apr 26;44(16):6269-75. doi: 10.1021/bi050124u.

Abstract

It is commonly assumed that urea denatures proteins by promoting backbone disorder, resulting in random-coil behavior. Indeed, it has been demonstrated that highly denatured proteins obey random-coil statistics. However, the random-coil model is specified by the global geometric properties of a polymeric chain and does not preclude locally ordered backbone structure. While urea clearly disfavors a compact native structure, it is not clear that the resulting backbone conformations are disordered. Using circular dichroism (CD) spectroscopy, we demonstrate that urea promotes formation of left-handed polyproline II (P(II)) helical structures in both short peptides and denatured proteins. The observed increase in P(II) content is sequence-dependent. These data indicate that denatured states possess significant amounts of locally ordered backbone structure. It is time for the formulation of new denatured-state models that take into account the presence of significant local backbone structure. Criteria for such models are outlined.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Circular Dichroism
  • In Vitro Techniques
  • Oligopeptides / chemistry
  • Oligopeptides / drug effects
  • Peptides / chemistry*
  • Peptides / drug effects*
  • Protein Denaturation / drug effects
  • Protein Structure, Secondary / drug effects
  • Proteins / chemistry
  • Proteins / drug effects
  • Urea / pharmacology*

Substances

  • Oligopeptides
  • Peptides
  • Proteins
  • polyproline
  • Urea