The Conformation of Histone H5

Abstract

Treatment of chicken erythrocyte histone H5 with trypsin in a high-ionic-strength medium results in very rapid initial digestion and the formation of a limiting resistant product peptide. Under these solution conditions the H5 molecule is maximally folded by spectroscopic criteria. The resistant peptide, GH5, probably represents a globular folded region of the molecule while the rapidly digested parts are disordered. The peptide GH5 is shown to comprise the sequence 22-100. In support of this conclusion it is shown that while intact histone H5 is hydrodynamically far from being a compact globular shape, peptide GH5 is approximately spherical by hydrodynamic and scattering criteria. Peptide GH5 retains all the .alpha.-helical structure of intact H5 (circular dichroism) and appears to also maintain all the tertiary structure (NMR). In solution at high ionic strength, histone H5 probably consists of 3 domains: an N-terminal disordered region 1-21, a compact globular central domain 22-100 and a long disordered C-terminal chain 101-185. Structural parallels are drawn with the 3-domain structure of the histone H1 molecule.