How does protein synthesis give rise to the 3D-structure?

Area of Science:

• Biochemistry and Molecular Biology
• Protein Dynamics and Structure

Background:

• Understanding protein folding pathways is crucial for comprehending protein function and misfolding diseases.
• Previous models proposed various mechanisms for how polypeptide chains attain their native three-dimensional structures.

Purpose of the Study:

• To review recent experimental data concerning the stages and kinetic intermediates in protein folding.
• To evaluate the consistency of new findings with the established 'framework model' of protein folding.
• To discuss the thermodynamic versus kinetic control of native protein structure formation.

Main Methods:

• Review and synthesis of recent experimental findings on protein folding intermediates.
• Theoretical analysis of the 'framework model' in light of new experimental evidence.
• Evaluation of thermodynamic and kinetic control hypotheses based on available data.

Main Results:

• Experimental data align with the 'framework model,' which posits a sequential folding pathway: secondary structure → molten globule state → native state.
• The framework model suggests that previously formed structural elements are not altered in subsequent folding stages.
• Analysis indicates that native structures of small proteins are likely under thermodynamic control, representing global free energy minima.

Conclusions:

• The framework model provides a robust explanation for observed protein folding pathways.
• Protein folding is a staged process where intermediate structures are progressively refined.
• Thermodynamic control, rather than kinetic control, is likely dominant in determining the final native state of small proteins.