BIPARTITE STRUCTURE OF THE ALPHA-LACTALBUMIN MOLTEN GLOBULE

Molten globules are thought to be general intermediates in protein-fol ding. Apparently conflicting studies have failed to clarify whether on e of the best characterized molten globules, that of alpha-lactalbumin , resembles an expanded native-like protein or a nonspecific collapsed polypeptide. Here we show that the molten globule properties of alpha -lactalbumin are largely confined to one of its two domains. The alpha -helical domain forms a helical structure with a native-like tertiary fold, while the beta-sheet domain is largely unstructured. Molten glob ules thus possess a native-like backbone topology, but this topology d oes not necessarily encompass the entire polypeptide chain. Our studie s indicate that molten globules provide an approximate solution to, an d considerable simplification of the protein folding problem.