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Protein structural effects of agonist binding to the nicotinic acetylcholine receptor
Author(s) -
Castresana Jose,
Fernandez-Ballester Gregorio,
Fernandez Asia M.,
Laynez Jose L.,
Arrondo Jose-Luis R.,
Ferragut Jose A.,
Gonzalez-Ros Jose M.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80967-l
Subject(s) - agonist , chemistry , cholinergic , acetylcholine receptor , biophysics , nicotinic acetylcholine receptor , nicotinic agonist , acetylcholine , crystallography , receptor , endocrinology , biochemistry , biology
The effects on the protein structure produced by binding of cholinergic agonists to purified acetylcholine receptor (AcChR) reconstituted into lipid vesicles, has been studied by Fourier‐transform infrared spectroscopy and differential scanning calorimetry. Spectral changes in the conformationally sensitive amide 1 infrared band indicates that the exposure of the AcChR to the agonist carbamylcholine, under conditions which drive the AcChR into the desensitized state, produces alterations in the protein secondary structure. Quantitative estimation of these agonist‐induced alterations by band‐fitting analysis of the amide 1 spectral band reveals no appreciable changes in the percent of α‐helix, but a decrease in β‐sheet structure, concomitant with an increase in less ordered structures. Additionally, agonist binding results in a concentration‐dependent increase in the protein thermal stability, as indicated by the temperature dependence of the protein infrared spectrum and by calorimetric analysis, which further suggest that AcChR desensitization induced by the cholinerpic agonist implies significant rearrangements in the protein structure.