Stabilization of a type VI turn in a family of linear peptides in water solution

Academic Article
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publication date

  • 1994

abstract

  • The sources of the stability of a type VI turn formed with high population in the cis isomeric form of an unblocked six residue peptide, Ser1-Tyr2-Pro3-Tyr4-Asp5-Val6 (SYPYDV), were investigated by making extensive amino acid substitutions at residues 2, 4 and 5. Several NMR parameters indicate the presence of the turn, including significant upfield shifts of the proton resonances of the cis proline, a small 3JHN alpha coupling constant for residue 2, a cross-turn d alpha N(i,i+2) from residue 2 to residue 4 and in increased mole fraction of the cis form in the conformational ensemble. By these criteria, a number of peptides were found to contain significant populations of type VI turn conformers in the cis form of the peptide. The NMR parameters are highly dependent on the sequence of the peptide, and are strongly correlated with each other and with the population of type VI turn. The greatest populations of turn conformations were observed for peptides of the general form AA-Ar-Pro-Ar-Hp, where AA represents any amino acid, Ar an aromatic residue and Hp a small hydrophilic residue. There is no evidence in the form of lowered amide proton temperature coefficients for direct hydrogen bonding as a primary source of turn stability. Instead, the major stabilizing factor, indicated by the strong dependence of the turn population on the presence of aromatic (not hydrophobic) residues at positions 2 and 4, is the stacking of the aromatic and proline rings. A measurable preference for deprotonated aspartate at position 5, which is not part of the turn itself, and the destabilization of the turn at high and low pH, indicate that electrostatic interactions between the unblocked N terminus and the aspartate carboxyl group also act to stabilize the turn conformation when the Ar-Pro-Ar sequence is present. Implications for stabilization of local elements of secondary structure during the earliest events in protein folding are discussed.