THE FOLDING OF HEN LYSOZYME INVOLVES PARTIALLY STRUCTURED INTERMEDIATES AND MULTIPLE PATHWAYS

Analysis of the folding of hen lysozyme shows that the protein does not become organized in a single cooperative event but that different parts of the structure become stabilized with very different kinetics. In particular, in most molecules the alpha-helical domain folds faster than the beta-sheet domain. Furthermore, different populations of molecules fold by kinetically distinct pathways. Thus, folding is not a simple sequential assembly process but involves parallel alternative pathways, some of which may involve substantial reorganization steps.