In vitro evolution of thermodynamically stable turns.
To determine the role of primary structure in specifying turns, random sequences (guests) were substituted for the native turn sequences in a series of proteins (hosts) of differing thermodynamic stabilities.The fraction of inserts that result in active proteins is measured as a function of the stability of the host and temperature. With a highly stable host, more than half of the inserts give functional proteins. However, a smaller fraction of sequences supports folding as the stability of the host decreases, and the temperature increases. The sequences of many of the selected inserts resemble the wild-type turn, and those that diverge match other established turn preferences. Thermodynamic measurements show that turn sequences selected under stringent conditions result in the most stable proteins. Thus, beta-turns appear to be under evolutionary pressure favouring thermodynamically stable structures.
Zhou
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DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0336, USA.
Hoess
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DeGrado
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D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D005075:Biological Evolution; D015723:Gene Library; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA; D013816:Thermodynamics
D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D011994:Recombinant Proteins