THE N-TERMINAL SEQUENCE (5-20) OF THYMOSIN BETA-4 BINDS TO MONOMERIC ACTIN IN AN ALPHA-HELICAL CONFORMATION

The relationship between the conformation of a peptide in solution and its interaction capacity is generally unclear. Trifluoroethanol (TFE) , which stabilizes alpha-helical conformations, can be used to induce definite folding in synthetic peptides. The N-terminal part of thymosi n beta 4, including the 5-20 sequence, is implicated in binding to mon omeric actin. The corresponding peptide was synthesized and its confor mation studied by CD. The peptide is unstructured in solution, and bec omes folded at medium TFE concentrations, below 30%. In contrast, TFE does not significantly modify the conformation of monomeric actin whic h conserves its intrinsic properties, such as gelsolin interaction and DNase-I inactivation. We report here that the apparent affinity of th e synthetic peptide to monomeric actin is increased by an order of mag nitude in the presence of TFE, which implies that the peptide adopts a folded conformation needed for accurate interaction. (C) 1996 Academi c Press, Inc.