The nature of protein folding pathways

Area of Science:

• Biochemistry
• Structural Biology
• Biophysics

Background:

• The protein folding problem has been studied for 50 years.
• Previous models suggested proteins fold in a two-state manner.
• Experimental evidence indicates a more complex folding process.

Purpose of the Study:

• To review advances in understanding protein folding.
• To emphasize the role of structural information in folding.
• To reconcile existing protein folding models.

Main Methods:

• Integration of historical and recent experimental data.
• Analysis of protein structural information.
• Examination of protein behavior under native and destabilized conditions.

Main Results:

• Proteins are multistate objects, not two-state.
• Proteins comprise cooperative foldon building blocks (approx. 20 residues).
• Foldons unfold and refold as units, resolving the Levinthal paradox.

Conclusions:

• Foldon units and their interactions guide stepwise protein folding.
• This model reconciles the 'new view' and 'defined pathway' models.
• Understanding foldons answers fundamental questions about protein folding mechanisms.