A PROTEIN DISSECTION STUDY OF A MOLTEN GLOBULE

Proteins have many distinct tertiary folds (Richardson, J. S. (1981) A dv. Prot. Chem. 34, 167-339). The term tertiary fold refers to the spa tial organization of secondary structure elements (alpha-helices and b eta-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-lactalbu min. Formation of this nativelike fold does not require extensive, spe cific side-chain packing. Our results suggest that much of the informa tion transfer from one-dimension to three-dimensions has occurred at t he molten globule stage of protein folding.