O‧‧‧C═O interaction, its occurrence and implications for protein structure and folding

Area of Science:

• Protein structure and folding
• Biophysics
• Structural biology

Background:

• Protein native structure is stabilized by various noncovalent interactions.
• Previously, a short-range N-H‧‧‧N hydrogen bond between adjacent peptide groups was observed.
• The role of the carbonyl moiety in such interactions was less understood.

Purpose of the Study:

• To investigate the involvement of the carbonyl moiety in short-range peptide group interactions.
• To explore the structural motifs and conformational preferences associated with these interactions.
• To understand the contribution of these interactions to protein secondary structure formation and protein folding.

Main Methods:

• Analysis of protein structural data to identify O‧‧‧C═O interactions between adjacent peptide groups.
• Characterization of backbone conformational angles and associated structural motifs (e.g., γ-turn, polyproline II helix).
• Examination of residue propensities and proximity to secondary structures.

Main Results:

• The carbonyl moiety participates in O‧‧‧C═O interactions, analogous to N-H‧‧‧N hydrogen bonds.
• Distinct backbone conformational clusters associated with the interacting residues were identified, forming motifs like γ-turns and polyproline II helices.
• These interactions are prevalent in irregular protein regions and contribute to β-turn formation and helix capping.

Conclusions:

• The O‧‧‧C═O interaction is a significant short-range force in protein structure stabilization.
• These interactions exemplify hierarchical growth of protein secondary structures, crucial for understanding protein folding.
• The findings highlight the importance of carbonyl interactions in helix termini capping, in addition to their role in α-helices.