Protein anatomy: spontaneous formation of filamentous helical structures from the N-terminal module of barnase.

Abstract

This paper reports the conformation of the N-terminal module (24 amino acid residues) of barnase in aqueous solution. This module contains the first of three helices in the intact protein. Circular dichroism spectra showed the peptide fragment to have a predominantly random coil structure immediately following dissolution in aqueous solution and to be gradually converted to a helical structure at 5 degrees C. This was mediated by aggregation, and an electron micrograph indicated the aggregate to be comprised of filamentous helical structures. Scanning tunneling microscopy showed the filamentous structures to be made up of protofilamentous structures containing many disks apparently stacked on top of each other. A monomer of the peptide predominantly took on a random coil conformation in aqueous solution and the multimer, a stable helical structure. A local amino acid sequence would thus appear to determine the secondary structure corresponding to that in a native protein but stability to be governed by other factors such as tertiary interactions. Helical wheel representation indicated the peptide fragment to have the features of an amphiphilic helix. Hydrophobic burial may provide the driving force for producing a stable helical structure in aqueous solution.