A Raman spectroscopic study of acctylcholine receptor-rich membranes from Torpedo marmorata. Interaction of the receptor with carbamylcholine and ( + )-tubocurarine

Structure of both the ligand- and lipid-dependent channel-inactive states of the nicotinic acetylcholine receptor probed by FTIR spectroscopy and hydrogen exchange

“…The main goal of the present study was to clarify the nature of the structural changes that lead to the formation of the channel-inactive state(s) of the nAChR upon either prolonged exposure to agonist (desensitization) or reconstitution into synthetic lipid membranes lacking cholesterol and anionic lipids. Several studies using a wide variety of techniques have been unable to detect a global change in structure upon Carb-induced desensitization (Mielke & Wallace, 1988;McCarthy & Stroud, 1989;Wu et al, 1990;Butler & McNamee, 1993;Aslanian et al, 1993;Méthot et al, 1994), The Carb-induced conformational change in the peptide backbone detected by FTIR difference spectroscopy is restricted to relatively few amino acid residues (Baenziger et al, 1993). In contrast, a substantial rearrangement in the secondary structure of affinity-purified nAChR has been detected by others both in the presence of Carb (Castresana et al, 1992;Fernandez-Ballester et al, 1994) and upon reconstituted into lipid membranes lacking either cholesterol and/or anionic lipids (Fong & McNamee, 1987; Butler & McNamee, 1993; Fernandez-Ballester et al, 1994).…”

“…Most FTIR spectra recorded in the presence or absence of Carb are essentially identical, suggesting that the global secondary structure is unaffected and that desensitization results from a subtle change in structure of the nAChR (Butler & McNamee, 1993;Méthot et al, 1994). The lack of a large change in secondary structure in the desensitized state is supported by CD (Mielke & Wallace, 1988;Wu et al, 1990), hydrogen-tritium exchange (McCarthy & Stroud, 1989), and Raman spectroscopy (Aslanian et al, 1993). The Carb-induced change in the peptide backbone detected by FTIR difference spectroscopy is restricted to relatively few amino acid residues (Baenziger et al, 1993).…”