Amino acid residues forming the interface of a neuronal nicotinic acetylcholine receptor with κ-bungarotoxin: A study using single residue substituted peptide analogs

doi:10.1016/0006-291X(91)90882-8

Biochemical and Biophysical Research Communications

Volume 176, Issue 1, 15 April 1991, Pages 11-17

https://doi.org/10.1016/0006-291X(91)90882-8 Get rights and content

Abstract

κ-Bungarotoxin is a high affinity antagonist of neuronal nicotinic acetylcholine receptors of the α3 subtype. Three sequence segments of the α3 subunit that contribute to forming the binding site for κ-bungarotoxin were previously located using synthetic peptides corresponding to the complete α3 subunit, i.e., α3(1–18), α3(50–71) and α3(180–201). Here we use single residue substituted peptide analogs of the α3(50–71) sequence, in which amino acids are sequentially replaced by Gly, to determine which residues are important for κ-bungarotoxin binding activity. Although no single substitution obliterated κ-bungarotoxin binding, several amino acid substitutions lowered the affinity for κ-bungarotoxin — i.e., two negatively charged residues (Glu51 and Asp62), and several aliphatic and aromatic residues (Leu54, Leu56, and Tyr63). These results indicate that the interface of the α3 subunit with κ-bungarotoxin involves primarily hydrophobic interactions, and a few negatively charged residues.

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Amino acid residues forming the interface of a neuronal nicotinic acetylcholine receptor with κ-bungarotoxin: A study using single residue substituted peptide analogs

Abstract

Pharmac. Ther

Neuroscience

Brain Res

Neuroscience

Brain Res

Trends Neurosci

Neuroscience

Neurosci. Lett

Cell

J. Biol. Chem

Neuron

J. Biol. Chem

Neuron

Neuron

Neuron

Neuron

J. Biol. Chem

J. Biol. Chem

J. Biol. Chem

Anal. Biochem

Brain Res

J. Neurosci

Mol. Neurobiol