title: Infrared study of the stability and folding kinetics of a series of β-hairpin peptides with a common NPDG turn.
abstract: The thermal stability and folding kinetics of a series of 15-residue β-hairpins with a common Type I [3:5] NPDG turn were studied using Fourier transform infrared spectroscopy (FTIR) and laser-induced temperature jump (T-jump) with infrared detection, respectively. Mutations at positions 3, 5, or 13 in the peptide sequence SEXYXNPDGTWTXTE, where X represents the position of mutation, were performed to study the roles of hydrophobic interactions in determining the thermodynamic and kinetic properties of β-hairpin folding. The thermal stability studies show a broad thermal folding/unfolding transition for all the peptides. T-jump studies indicate that these β-hairpin peptides fold in less than 2 μs. In addition, both folding and unfolding rate constants decrease with increasing strength of hydrophobic interactions. Kinetically, the hydrophobic interactions have more significant influence on the unfolding rate than the folding rate. Φ-value analysis indicates that the hydrophobic interactions between the side chains are mainly formed at the latter part of the transition-state region during the folding process. In summary, the results suggest that the formation of the native structure of these β-hairpins depends on the correct topology of the hydrophobic cluster. Besides the formation of the turn region as a key process for folding as suggested by previous studies, a hydrophobic collapse process may also play a crucial role during β-hairpin folding.
authors.affiliation: Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xu
authors.forename: Deguo
authors.initials: D
authors.lastname: Du
authors.forename: Rolando
authors.initials: R
authors.lastname: Oyola
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D057927:Hydrophobic and Hydrophilic Interactions; D055029:Inverted Repeat Sequences; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D010455:Peptides