Journal of Molecular Biology vol:246 issue:3 pages:382-7
Temperature-induced unfolding of human lysozyme has been monitored by circular dichroism and by nuclear magnetic resonance experiments at a variety of low pH values. The results indicate that, although at pH values above 3 unfolding appears to be consistent with a two-state model, at lower pH values this is not the case. At pH 1.2, for example, unfolding of the tertiary structure occurs at a temperature approximately 10 deg. C lower than that of the secondary structure. At 60 degrees C there is no detectable native tertiary structure remaining for human lysozyme at pH 1.2, although far-UV CD results show preservation of some 40% of the signal attributable to alpha-helical elements in the protein. This indicates the existence of a partially folded state of human lysozyme at low pH that has at least some characteristics of the well-defined molten globule state of the homologous alpha-lactalbumins and of the kinetic intermediates observed in the folding of alpha-lactalbumins and of c-type lysozymes. These results suggest that the absolute distinction between these two groups of proteins in terms of their different unfolding behaviour is not valid, and provide insights into possible features stabilizing such states.