Solution structure of αtα, a helical hairpin peptide of de novo design

Abstract

αtα is a 38-residue peptide designed to adopt a helical hairpin conformation in solution (Fezoui Y, Weaver DL, Osterhout JJ, 1995, Protein Sci 4:286-295). A previous study of the carboxylate form of αtα by CD and two-dimensional NMR indicated that the peptide was highly helical and that the helices associated in approximately the intended orientation (Fezoui Y, Weaver DL, Osterhout JJ, 1994, Proc Natl Acad Sci USA 91:3675-3679). Here, the solution structure of αtα as determined by two-dimensional NMR is reported. A total of 266 experimentally derived distance restraints and 20 dihedral angle restraints derived from J-couplings were used. One-hundred initial structures were generated by distance geometry and refined by dynamical simulated annealing. Twenty-three of the lowest-energy structures consistent with the experimental restraints were analyzed. The results presented here show that αtα is comprised of two associating helices connected by a turn region.