Cation-π interactions in protein-protein interfaces

Arginine is an abundant residue in protein-protein interfaces. The importance of this residue relates to the versatility of its side chain in intermolecular interactions. Different classes of protein-protein interfaces were surveyed for cation-π interactions. Approximately half of the protein complexes and one-third of the homodimers analyzed were found to contain at least one intermolecular cation-π pair. Interactions between arginine and tyrosine were found to be the most abundant. The electrostatic interaction energy was calculated to be ∼3 kcal/mol, on average. A distance-based search of guanidinium:aromatic interactions was also performed using the Macromolecular Structure Database (MSD). This search revealed that half of the gnanidinium:aromatic pairs pack in a coplanar manner. Furthermore, it was found that the cationic group of the cation-π pair is frequently involved in intermolecular hydrogen bonds. In this manner the arginine side chain can participate in multiple interactions, providing a mechanism for inter-protein specificity. Thus, the cation-π interaction is established as an important contributor to protein-protein interfaces.