Effect of a single aspartate on helix stability at different positions in a neutral alanine-based peptide.
A single aspartate residue has been placed at various positions in individual peptides for which the alanine-based reference peptide is electrically neutral, and the helix contents of the peptides have been measured by circular dichroism. The dependence of peptide helix content on aspartate position has been used to determine the helix propensity (s-value). Both the charged (Asp-) and uncharged (Asp0) forms of the aspartate residue are strong helix breakers and have identical s-values of 0.29 at 0 degree C. The interaction of Asp- with the helix dipole affects helix stability at positions throughout the helix, not only near the N-terminus, where the interaction is helix stabilizing, and the C-terminus, where it is destabilizing. Comparison of the helix contents at acidic pH (Asp0) and at neutral pH (Asp-) shows that the charge-helix dipole interaction is screened slowly with increasing NaCl concentration, and screening is not complete even at 4.8 M NaCl. Lastly, a helix-stabilizing hydrogen-bond interaction between glutamine and aspartate (spacing i, i + 4) has been found. This side-chain interaction is specific for both the orientation and spacing of the glutamine and aspartate residues and is resistant to screening by NaCl.
Huyghues-Despointes
B M
BM
Department of Biochemistry, Stanford University School of Medicine, California 94305.
Scholtz
J M
JM
Baldwin
R L
RL
D000409:Alanine; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry*; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology
D010455:Peptides; D001224:Aspartic Acid; D012965:Sodium Chloride; D000409:Alanine