Sodium dodecyl sulfate- and carbamylcholine-induced changes in circular dichroism spectra of acetylcholine receptor synthetic peptides.
The effect of sodium dodecyl sulfate (SDS) on the conformation of acetylcholine receptor alpha-subunit synthetic peptides was investigated by circular dichroism. In the presence of SDS (0.01-0.02%), the affinity of a 173-204 32 residue peptide and a 172-227 56 residue peptide for the competitive antagonist alpha-bungarotoxin increases about 10-fold to the nanomolar range. Circular dichroism spectroscopy of these peptides revealed significant changes in the secondary structure of the peptides in the presence of SDS at concentrations below the critical micelle concentration. It is concluded that SDS induces a conformation of the peptides that is conductive to high affinity binding. Carbamylcholine, an acetylcholine analog, produced small but significant changes in the spectrum of the 173-204 peptide. This change could be the result of agonist-induced conformational changes in this region of the acetylcholine receptor alpha-subunit or to changes in the asymmetric environments of aromatic chromophores in the binding site. These studies demonstrate that synthetic peptides alone are capable of retaining significant functional activity and contain significant secondary structure.
Donnelly-Roberts
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Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
Lentz
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D000595:Amino Acid Sequence; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002942:Circular Dichroism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000187:drug effects*; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology*; D014101:Torpedo
D002038:Bungarotoxins; D046911:Macromolecular Substances; D010446:Peptide Fragments; D010455:Peptides; D011950:Receptors, Cholinergic; D012967:Sodium Dodecyl Sulfate; D002217:Carbachol