DOES THE MOLTEN GLOBULE HAVE A NATIVE-LIKE TERTIARY FOLD

One of the mysteries in protein folding is how folding intermediates d irect a protein to its unique final structure. To address this questio n, we have studied the molten globule formed by the alpha-helical doma in of alpha-lactalbumin (alpha-LA) and demonstrated that it has a nati ve-like tertiary fold, even in the absence of rigid, extensive side ch ain packing. These studies suggest that the role of molten globule int ermediates in protein folding is to maintain an approximate native bac kbone topology while still allowing minor structural rearrangements to occur.