Osmolyte effects on helix formation in peptides and the stability of coiled-coils.
The ability of several naturally occurring substances known as osmolytes to induce helix formation in an alanine-based peptide have been investigated. As predicted by the osmophobic effect hypothesis, the osmolytes studies here do induce helix formation. Trimethylamine-N-oxide (TMAO) is the best structure-inducing osmolytes investigated here, but it is not as effective in promoting helix formation as the common cosolvent trifluoroethanol (TFE). We also provide a semiquantitative study of the ability of TMAO to induce helix formation and urea, which acts as a helix (and protein) denaturant. We find that on a molar basis, these agents are exactly counteractive as structure inducing and unfolding agents. Finally, we extend the investigations to the effects of urea and TMAO on the stability of a dimeric coiled-coil peptide and find identical results. Together these results support the tenets of the osmophobic hypothesis and highlight the importance of the polypeptide backbone in protein folding and stability.
Celinski
Scott A
SA
Department of Medical Biochemistry & Genetics, Center for Advanced Biomolecular Research, Texas A&M University, College Station 77843-1114, USA.
Scholtz
J Martin
JM
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D004268:DNA-Binding Proteins; D019281:Dimerization; D016350:Leucine Zippers / Q000187:drug effects*; D008744:Methylamines / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D011489:Protein Denaturation; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary / Q000187:drug effects; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D014270:Trifluoroethanol / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D008744:Methylamines; D029701:Saccharomyces cerevisiae Proteins; D014270:Trifluoroethanol; D014508:Urea; D011494:Protein Kinases; C005855:trimethyloxamine; D000409:Alanine