Helix-stabilizing nonpolar interactions between tyrosine and leucine in aqueous and TFE solutions: 2D-1H NMR and CD studies in alanine-lysine peptides.
Interactions between side chains spaced (i,i + 3) and (i,i + 4) may explain the context dependence of helix propensities observed in different systems. Nonpolar residues with these spacings occur frequently in protein helices and stabilize isolated peptide helices. Here (i,i + 3) and (i,i + 4) nonpolar interactions between Tyr and Leu in different solution conditions are studied in detail in alanine-based peptides using 2D 1H NMR and CD spectroscopy. Helix contents analyzed using current models for helix-coil transitions yield interaction energies which demonstrate significant helix stabilization in aqueous 1 M NaCl solutions by Tyr-Leu or Leu-Tyr pairs when spaced (i,i + 4) and, to a smaller extent, when spaced (i,i + 3), comparable to those estimated for other residue pairs. The interactions persist in solutions containing TFE, a helix-stabilizing solvent believed to diminish hydrophobic interactions, but not in helix-destabilizing 6 M urea. 1H NMR resonances for all peptides and solution conditions except in 6 M urea were completely assigned. NMR data indicate that the N-terminal residues are more helical and that the N-acetyl group participates in helix formation. The two (i,i + 4) spaced pairs show the same pattern of NOE cross-peaks between the Tyr and Leu side chains, as do the two (i,i + 3) pairs in 1 M NaCl as well in TFE solutions, and correspond well with that expected for the specific Tyr-Leu pair with side-chain contacts in protein helices.
Padmanabhan
S
S
Instituto de Estructura de la Materia, Consejo Superior de Investigaciones Cientificas, Madrid, Spain. empadhu@rocky2.roca.csic.es
Jiménez
M A
MA
Laurents
D V
DV
Rico
M
M
D000409:Alanine / Q000737:chemistry*; D002942:Circular Dichroism; D007930:Leucine / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012965:Sodium Chloride; D012996:Solutions; D014270:Trifluoroethanol; D014443:Tyrosine / Q000737:chemistry*
D009842:Oligopeptides; D012996:Solutions; D014443:Tyrosine; D012965:Sodium Chloride; D014270:Trifluoroethanol; D007930:Leucine; D008239:Lysine; D000409:Alanine