CONFORMATIONAL ANALYSIS OF FRAGMENT OF HUMAN PIN1 WW DOMAIN: INFLUENCE OF CHARGED AMINO-ACID RESIDUES ON β-HAIRPIN STRUCTURE

Abstract

We examined the effect of like-charged residues on the conformation of an original nine amino-acid-residue fragment of the human Pin1 WW domain (hPin1) with the following sequence: Ac-Arg-Met-Ser-Arg-Ser-Ser-Gly-Arg-Val-NH₂ (U9). This was facilitated by CD and NMR spectroscopic measurements, and molecular dynamics calculations. Our earlier studies suggested that the presence of like charged residues at the end of a short polypeptide chain composed of nonpolar residues could induce a chain reversal. For the U9 peptide, canonical MD simulations with NMR-derived restraints demonstrated the presence of ensembles of structures with a tendency to form a β-chain reversal. Additionally, thermal stabilities of the peptide under study were measured using differential scanning calorimetry (DSC). The estimated well defined phase transition point showed that conformational equilibria in the U9 peptide were strongly dependent on temperature.