Abundance of Glycine-mediated O···C=O, N–H···N, and Cα–H···O Interactions in Homo- and Hetero-oligomeric Protein Complexes

Abstract

Glycines are considered the most flexible among all residues, can fit anywhere, and are typically found in short loops and turns. Their specific roles in protein folding and binding have been largely overlooked. Here, we investigate the presence of key noncovalent interactions, O···C=O and N–H···N, that are mediated by Gly between two peptide groups at the interface of oligomeric proteins. These are put in context relative to another weak interaction, viz., C^α–H···O. Also, these include interactions where both of the interacting residues are Gly or where either of them is a Gly. We found an enrichment of all of the Gly···Gly-mediated interactions at the interfaces, irrespective of the nature of the complex, whether obligate, transient, or a heterodimer. Comparatively, a higher propensity of Gly···Gly O···C=O interactions is found at the obligate homodimer interfaces. We also noted that 10% of the Gly residues at the obligate homodimer interfaces are involved in the O···C=O interactions, 1% is involved in the N–H···N, and 22% are involved in C^α–H···O interactions. Interestingly, in the weakly associated transient dimers too, 40% of the total interface Gly residues are involved in any of the three interactions. We noted a secondary structure preference for the Gly···Gly-mediated O···C=O interactions in obligate dimers, which are predominantly from helical segments. These nonclassical interactions may contribute to the function of Gly-rich regions in proteins.