The Role of Aromatic Residues in Stabilizing the Secondary and Tertiary Structure of Avian Pancreatic Polypeptide

Abstract

Avian Pancreatic Polypeptide is a 36 residue protein that exhibits a tertiary fold. Results of previous experimental and computational studies indicate that the structure of aPP is stabilized more by non-bonded interactions than by the hydrophobic effect. Aromatic residues are known to participate in a variety of long range non-bonded interactions, with both backbone atoms and the atoms of other side-chains, which could be responsible, in part, for the stability of both the local secondary structure and the tertiary fold. The effect of these aromatic interactions on the stability of aPP was calculated using BHandHLYP/cc-pVTZ. Aromatic residues were shown to participate in multiple hydrogen bonded and weakly polar interactions in the secondary structure. The energies of the weakly polar interactions are comparable with those of hydrogen bonds. Aromatic residues were also shown to participate in multiple weakly polar interactions across the tertiary fold, again with energies similar to those of hydrogen bonds.

Fig. 1

A. Backbone structure of aPP with interacting side chains and backbone atoms displayed. The N-terminal PPII helix is magenta, the turn structure is green and the α-helix is dark blue. B. The primary structure of aPP, interacting residues are in boldface.

Fig. 2

Structure of the PPII_frag and α_frag. The color scheme is the same as Figure 1 except that the Gly residues which replace residues Phe20 and Tyr27 are red.

Fig. 3

Hydrogen bonds of residues Pro8Gly9 and Ala12. The hydrogen bond is indicated with a dashed line, and the three non-canonical CH..O hydrogen bonds are indicated with solid lines.