STRUCTURE OF HISACTOPHILIN IS SIMILAR TO INTERLEUKIN-1-BETA AND FIBROBLAST GROWTH-FACTOR

THE fast reaction of the actin-based cytoskeleton in motile cells after stimulation with a chemoattractant requires a signal-transduction chain that creates a very specific environment at distinct regions beneath the plasma membrane1. Dictyostelium hisactophilin, a unique actin-binding protein, is a submembranous pH sensor that signals slight changes of the H+ concentration to actin by inducing actin polymerization and binding to microfilaments only at pH values below seven2. It has a relative molecular mass of 13.5K and its most unusual feature is the presence of 31 histidine residues among its total of 118 amino acids. The transduction of an external signal from the plasma membrane to the cytoskeleton is poorly understood. Here we report the protein's structure in solution determined by nuclear magnetic resonance spectroscopy. The nuclear Overhauser effect intensities of the three-dimensional nuclear Overhauser spectra3,4 were used directly in the calculations5. The overall folding of hisactophilin is similar to that of interleukin-1beta6-9 and fibroblast growth factor10, but the primary amino-acid sequence of hisactophilin is unrelated to these two proteins.