title: Redesigning the hydrophobic core of a four-helix-bundle protein.
abstract: Rationally redesigned variants of the 4-helix-bundle protein Rop are described. The novel proteins have simplified, repacked, hydrophobic cores and yet reproduce the structure and native-like physical properties of the wild-type protein. The repacked proteins have been characterized thermodynamically and their equilibrium and kinetic thermal and chemical unfolding properties are compared with those of wild-type Rop. The equilibrium stability of the repacked proteins to thermal denaturation is enhanced relative to that of the wild-type protein. The rate of chemically induced folding and unfolding of wild-type Rop is extremely slow when compared with other small proteins. Interestingly, although the repacked proteins are more thermally stable than the wild type, their rates of chemically induced folding and unfolding are greatly increased in comparison to wild type. Perhaps as a consequence of this, their equilibrium stabilities to chemical denaturants are slightly reduced in comparison to the wild type.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114.
authors.forename: M
authors.initials: M
authors.lastname: Munson
authors.forename: R
authors.initials: R
authors.lastname: O'Brien
authors.forename: J M
authors.initials: JM
authors.lastname: Sturtevant
authors.forename: L
authors.initials: L
authors.lastname: Regan
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D002151:Calorimetry; D002942:Circular Dichroism; D019791:Guanidine; D006146:Guanidines; D007700:Kinetics; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D015202:Protein Engineering; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins; D013696:Temperature; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D006146:Guanidines; D016601:RNA-Binding Proteins; C054243:Rop protein, ColE1 plasmid; D012313:RNA; D019791:Guanidine