NATIVE-LIKE BETA-HAIRPIN STRUCTURE IN AN ISOLATED FRAGMENT FROM FERREDOXIN - NMR AND CD STUDIES OF SOLVENT EFFECTS ON THE N-TERMINAL-20 RESIDUES

The conformational properties of protein fragments have been widely st udied as models of the earliest initiation events in protein folding, While native-like alpha-helices and beta-turns have been identified, l ess is known about the factors that underly beta-sheet formation, in p articular beta-hairpins, where considerably greater long-range order i s required, The N-terminal 20 residue sequence of native ferredoxin I (from the blue-green alga Aphanothece sacrum) forms a beta-hairpin in the native structure and has been studied in isolation by NMR and CD s pectroscopy, Local native-like interactions alone are unable to stabil ize significantly a folded conformation of the 20-residue fragment in purely aqueous solution, However, we show that the addition of low lev els of organic co-solvents promotes formation of native-like beta-hair pin structure, The results suggest an intrinsic propensity of the pept ide to form a native-like beta-hairpin structure, and that the organic co-solvent acts in lieu of the stabilizing influence of tertiary inte ractions (probably hydrophobic contacts) which occur in the folding of the complete ferredoxin sequence, The structure of the isolated hairp in, including the native-like register of interstrand hydrogen bonding interactions, appears to be determined entirely by the amino acid seq uence, The solvent conditions employed have enabled this intrinsic pro perty to be established.