Limitations in ab initio protein structure prediction and design imply deficiencies in our understanding of the forces contributing to protein structure. Recent work has shown that backbone carbonyl groups can form additional interactions beyond canonical hydrogen bonds. For example, protein helices often benefit from stabilization by n→π* interactions between adjacent backbone carbonyl groups. Analogous interactions in β-sheets had not previously been identified, despite the ubiquity of this secondary structure. Here, we report the presence of a noncanonical hydrogen bond between the carbonyl oxygen and amide proton of the same residue within individual β-strands. These “C5” interactions share chemical and spectroscopic characteristics of traditional hydrogen bonds despite their distorted geometry. Direct perturbation of these interactions alters the global thermal stability of β-sheet models, and examples of C5 hydrogen bonds are detected in 94% of proteins, affecting approximately 5% of all residues. These hydrogen bonds may bias the backbone toward the amyloid state in particular. Our results therefore motivate further study of how protein side chains mitigate the conformational preferences of the backbone. Finally, incorporation of these and other secondary interactions into computational energy functions presents an opportunity for the improvement of biochemical modeling.

Backbone C5 hydrogen bonds in proteins

253rd National Meeting (2017)

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