Controlling peptide folding with repulsive interactions between phosphorylated amino acids and tryptophan.
Phosphorylated amino acids were incorporated into a designed beta-hairpin peptide to study the effect on beta-hairpin structure when the phosphate group is positioned to interact with a tryptophan residue on the neighboring strand. The three commonly phosphorylated residues in biological systems, serine, threonine, and tyrosine, were studied in the same beta-hairpin system. It was found that phosphorylation destabilizes the hairpin structure by approximately 1.0 kcal/mol, regardless of the type of phosphorylated residue. In contrast, destabilization due to glutamic acid was about 0.3 kcal/mol. Double mutant cycles and pH studies are consistent with a repulsive interaction as the source of destabilization. These findings demonstrate a novel mechanism by which phosphorylation may influence protein structure and function.
Riemen
Alexander J
AJ
Department of Chemistry, CB 3290, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Waters
Marcey L
ML
D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D012694:Serine / Q000737:chemistry / Q000235:genetics; D013912:Threonine / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry* / Q000235:genetics; D014443:Tyrosine / Q000737:chemistry
D010455:Peptides; D010768:Phosphoserine; D013912:Threonine; D018698:Glutamic Acid; D014443:Tyrosine; D012694:Serine; D014364:Tryptophan