DISULFIDE-REARRANGED MOLTEN GLOBULE STATE OF ALPHA-LACTALBUMIN

A three-disulfide form of human cu-lactalbumin, with free thiols on Cy s6 and Cys120, can adopt the molten globule conformation. It then spon taneously rearranges its three disulfide bonds to many isomers that te nd to maintain the molten globule conformation. The distribution of fr ee thiol groups within the rearranged species has been determined quan titatively by chemical modification and peptide mapping. The protein's eight cysteine residues were modified with nearly equal frequencies, although there were significant departures from randomness. The result s confirm that the molten globule state of alpha-lactalbumin does not maintain the nativelike topology of the polypeptide backbone but is mo re like a collapsed form of an unfolded protein.