A Protein Dissection Study of a Molten Globule

Proteins have many distinct tertiary folds (Richardson, J. S. (1981) Adv. Prot. Chem. 34, 167-339). The term tertiary fold refers to the spatial organization of secondary structure elements (alpha-helices and beta-strands). It is not known when, in the process of protein folding, a native tertiary fold emerges. Here, we show that the helical domain of human alpha-lactalbumin, in isolation, forms a molten globule with the same overall tertiary fold as that found in intact alpha-lactalbumin. Formation of this native-like fold does not require extensive, specific side-chain packing. Our results suggest that much of the information transfer from one-dimension to three-dimensions has occurred at the molten globule stage of protein folding.