HOW IMPORTANT IS THE MOLTEN GLOBULE FOR CORRECT PROTEIN-FOLDING

The molten globule (MG) state is widely considered to be an important intermediate in protein folding and to have a polypeptide backbone wit h a native-like topology. The experimental evidence for this view was obtained largely, however, with MG proteins containing native-like con straints. When the four disulphide bonds of or-lactalbumin were allowe d to rearrange to those favoured by the MG, opposite conclusions were obtained. Consideration of all the experimental data indicates that an y tendency of this MG to be nativelike is negligible relative to all t he other topologies that it can adopt. Furthermore, the experimental d ata indicate that the MG is not the key to rapid protein folding.