CONTEXT IS A MAJOR DETERMINANT OF BETA-SHEET PROPENSITY

RESIDUES in B-sheets occur in two distinct tertiary contexts: central strands, bordered on both sides by other beta-strands, and edge strand s, bordered on only a single side by another beta-strand(1). The Delta Delta G values for beta-sheet formation measured at an edge beta-stra nd of the IgG-binding domain of protein G(GB1) are suite different fro m those obtained previously(2,3) at a central position in the same pro tein. In particular, there is no correlation at the edge position with statistically determined beta-sheet-forming preferences(4). The diffe rences between beta-sheet propensities measured at central and edge be ta-strands, Delta Delta Delta G values, correlate with the values of w ater/octanol transfer free energies(5) and side-chain non-polar surfac e area for the amino acids(6). These results strongly suggest that, un like alpha-helix formation, beta-sheet formation is determined in larg e part by tertiary context, even at solvent-accessible sites, and not by intrinsic secondary structure preferences.