Secondary structure transitions and aggregation induced in dynorphin neuropeptides by the detergent sodium dodecyl sulfate.
Dynorphins, endogeneous opioid neuropeptides, function as ligands to the opioid kappa receptors and also induce non-opioid effects in neurons, probably related to direct membrane interactions. We have characterized the structure transitions of dynorphins (big dynorphin, dynorphin A and dynorphin B) induced by the detergent sodium dodecyl sulfate (SDS). In SDS titrations monitored by circular dichroism, we observed secondary structure conversions of the peptides from random coil to alpha-helix with a highly aggregated intermediate. As determined by Fourier transform infrared spectroscopy, this intermediate exhibited beta-sheet structure for dynorphin B and big dynorphin. In contrast, aggregated dynorphin A was alpha-helical without considerable beta-sheet content. Hydrophobicity analysis indicates that the YGGFLRR motif present in all dynorphins is prone to be inserted in the membrane. Comparing big dynorphin with dynorphin A and dynorphin B, we suggest that the potent neurotoxicity of big dynorphin could be related to the combination of amino acid sequences and secondary structure propensities of dynorphin A and dynorphin B, which may generate a synergistic effect for big dynorphin membrane perturbing properties. The induced aggregated alpha-helix of dynorphin A is also correlated with membrane perturbations, whereas the beta-sheet of dynorphin B does not correlate with membrane perturbations.
Hugonin
Loïc
L
Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-10691, Stockholm, Sweden.
Barth
Andreas
A
Gräslund
Astrid
A
Perálvarez-Marín
Alex
A
D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003902:Detergents / Q000494:pharmacology*; D004399:Dynorphins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared
D000577:Amides; D003902:Detergents; D012967:Sodium Dodecyl Sulfate; D004399:Dynorphins