From propensities to patterns to principles in protein folding

Area of Science:

• Protein structure and dynamics
• Biophysics
• Molecular biology

Background:

• Globular proteins fold by filtering conformers with unsatisfied backbone hydrogen bonds.
• Unsatisfied hydrogen bonds are destabilizing, shifting the unfolded-native equilibrium.
• Repetitive secondary structures like alpha-helices and beta-sheets form cooperative hydrogen-bonded networks.

Purpose of the Study:

• To propose that beta-turns are essential for protein self-assembly.
• To elucidate the role of beta-turns in initiating the assembly of protein structural elements.
• To broaden the understanding of protein folding mechanisms.

Main Methods:

• The study is primarily theoretical, proposing a mechanism based on existing hypotheses and biophysical principles.
• Analysis of the structural and energetic contributions of beta-turns in protein folding.
• Comparison of the hydrogen bonding properties of beta-turns with repetitive secondary structures.

Main Results:

• Beta-turns, compact four-residue motifs, reverse protein chain direction and act as "hinges".
• Unlike repetitive secondary structures, beta-turns form autonomously and initiate the assembly of scaffold elements.
• This self-assembly mechanism leads to preorganization of the folding population and reduced folding entropy.

Conclusions:

• Beta-turns play an essential role in protein self-assembly by initiating the cooperative "zipping" of structural elements.
• The proposed mechanism highlights the importance of beta-turns in controlling protein conformation and folding.
• Understanding the role of beta-turns provides new insights into the fundamental principles of protein folding.