How important is the molten globule for correct protein folding?

Area of Science:

• Biochemistry
• Protein Folding Dynamics
• Structural Biology

Background:

• The molten globule (MG) state is traditionally viewed as a key intermediate in protein folding.
• This perspective is largely based on studies of MG proteins with native-like constraints.

Purpose of the Study:

• To re-evaluate the native-like topology of the molten globule state.
• To determine the role of the MG state in rapid protein folding.

Main Methods:

• Investigated alpha-lactalbumin's molten globule state.
• Allowed disulfide bonds to rearrange to favor MG topology.
• Analyzed experimental data on protein folding intermediates.

Main Results:

• Opposite conclusions were obtained when disulfide bonds rearranged.
• The MG state's native-like topology was found to be negligible.
• The MG state is not essential for rapid protein folding.

Conclusions:

• The molten globule state's topology is not significantly native-like.
• The molten globule state does not appear to be the key to rapid protein folding.