Carbohydrate-pi interactions: what are they worth?

Protein-carbohydrate interactions play an important role in many biologically important processes. The recognition is mediated by a number of noncovalent interactions, including an interaction between the alpha-face of the carbohydrate and the aromatic side chain of the protein. To elucidate this interaction, it has been studied in the context of a beta-hairpin in aqueous solution, in which the interaction can be investigated in the absence of other cooperative noncovalent interactions. In this beta-hairpin system, both the aromatic side chain and the carbohydrate were varied in an effort to gain greater insight into the driving force and magnitude of the carbohydrate-pi interaction. The magnitude of the interaction was found to vary from -0.5 to -0.8 kcal/mol, depending on the nature of the aromatic ring and the carbohydrate. Replacement of the aromatic ring with an aliphatic group resulted in a decrease in interaction energy to -0.1 kcal/mol, providing evidence for the contribution of CH-pi interactions to the driving force. These findings demonstrate the significance of carbohydrate-pi interactions within biological systems and also their utility as a molecular recognition element in designed systems.

Stabilization of the N-terminal beta-hairpin of ubiquitin by a terminal hydrophobic cluster.

Study of model beta-hairpin peptides allows for better understanding of the factors involved in the formation of beta-sheet secondary structure in proteins. It is known that turn sequence, sidechain-sidechain interactions, interstrand hydrogen bonding, and beta-sheet propensity of residues are all important for beta-hairpin stability in aqueous solution. However, interactions of the sidechains of the terminal residues of hairpins are thought to contribute little to overall hairpin stability since these residues are typically frayed. Here, the authors report a stabilizing hydrophobic cluster of residues at the termini of the naturally occurring excised N-terminal beta-hairpin of Ubiquitin that folds autonomously in aqueous solution. Our data show that deletion of Met1 and Val17 from this hairpin destabilized the folded state in both aqueous solution and in aqueous-methanol solutions. These results suggest that interactions of terminal residues which are usually frayed can nonetheless contribute significantly to overall stability of beta-hairpin.