title: The stabilizing effects of hydrophobic cores on peptide folding of bovine-pancreatic-trypsin-inhibitor folding-intermediate model.
abstract: A synthetic peptide model composed of alpha-helical and beta-sheet portions (P alpha P beta) is a crucial folding intermediate in the folding of bovine pancreatic trypsin inhibitor (BPTI), which contains 30 amino acid residues, and provides a good model for studying the folding structure. Using this model the roles of hydrophobic cores, such as non-polar amino acids and a short beta strand, in the folding structure stability were investigated by deleting the hydrophobic amino acids or substituting with Ala. As a first step, a mutant peptide, P alpha 6 P beta 1, was made by removing the four residues (NNFK46) from the N-terminus of P alpha which make a short beta strand in native BPTI, and each of the hydrophobic cores, Phe45 of P alpha and Tyr21 of P beta, were substituted by Ala. Without the short beta strand the peptide still folds in spite of its low solubility, suggesting that a simple alpha helix and central antiparallel beta sheet contain sufficient information to direct the folding of this region of molecule. The peptide without Tyr21 was much more unstable than P alpha 6 P beta 1, such that most of the folding structure collapsed even at 0 degree C, whereas without Phe45 the structure was more stable than P alpha 6 P beta 1. This indicates that the hydrophobic interactions of Tyr21 in P beta are more important in BPTI folding.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology.
authors.forename: D Y
authors.initials: DY
authors.lastname: Kwon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D007611:Aprotinin / Q000737:chemistry*; D002417:Cattle; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013696:Temperature
chemical_list: D007611:Aprotinin