title: Urea promotes polyproline II helix formation: implications for protein denatured states.
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.
authors.affiliation: Center for Structural Biology, Department of Molecular and Cellular Biochemistry, University of Kentucky, 800 Rose Street, Lexington, Kentucky 40536-0298, USA.
authors.forename: Shelly J
authors.initials: SJ
authors.lastname: Whittington
authors.forename: Brian W
authors.initials: BW
authors.lastname: Chellgren
authors.forename: Veronique M
authors.initials: VM
authors.lastname: Hermann
authors.forename: Trevor P
authors.initials: TP
authors.lastname: Creamer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000737:chemistry / Q000187:drug effects; D010455:Peptides / Q000737:chemistry* / Q000187:drug effects*; D011489:Protein Denaturation / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D011506:Proteins / Q000737:chemistry / Q000187:drug effects; D014508:Urea / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D010455:Peptides; D011506:Proteins; C011083:polyproline; D014508:Urea