STRUCTURAL CHARACTERIZATION OF A HIGHLY-ORDERED MOLTEN GLOBULE AT LOWPH

The characterization of unfolded and partly folded states of proteins is central to understanding protein stability and folding, as well as providing a basis for protein design. The four helix bundle-protein in terleukin-4 undergoes an unfolding transition at low ph. Using heteron uclear nuclear magnetic resonance methods we show that following this transition the protein retains a highly ordered hydrophobic core in wh ich most, but not all, of the secondary structure is preserved. Extens ive disorder exists, however, in regions of polypeptide chain linking the structural elements which make up this core. We suggest that this 'highly ordered molten globule' could be indicative of the type of str uctures occurring late in protein folding processes, in contrast to mo re disordered 'molten globules' which relate to early folding intermed iates.