Ryan_2001_J.Biol.Chem_276_4796

Reference

Title : A conformational intermediate between the resting and desensitized states of the nicotinic acetylcholine receptor - Ryan_2001_J.Biol.Chem_276_4796
Author(s) : Ryan SE , Blanton MP , Baenziger JE
Ref : Journal of Biological Chemistry , 276 :4796 , 2001
Abstract :

The structural changes induced in the nicotinic acetylcholine receptor by two noncompetitive channel blockers, proadifen and phencyclidine, have been studied by infrared difference spectroscopy and using the conformationally sensitive photoreactive noncompetitive antagonist 3-(trifluoromethyl)-3-m-([(125)I]iodophenyl)diazirine. Simultaneous binding of proadifen to both the ion channel pore and neurotransmitter sites leads to the loss of positive markers near 1663, 1655, 1547, 1430, and 1059 cm(-)(1) in carbamylcholine difference spectra, suggesting the stabilization of a desensitized conformation. In contrast, only the positive markers near 1663 and 1059 cm(-)(1) are maximally affected by the binding of either blocker to the ion channel pore suggesting that the conformationally sensitive residues vibrating at these two frequencies are stabilized in a desensitized-like conformation, whereas those vibrating near 1655 and 1430 cm(-)(1) remain in a resting-like state. The vibrations at 1547 cm(-)(1) are coupled to those at both 1663 and 1655 cm(-)(1) and thus exhibit an intermediate pattern of band intensity change. The formation of a structural intermediate between the resting and desensitized states in the presence of phencyclidine is further supported by the pattern of 3-(trifluoromethyl)-3-m-([(125)I]iodophenyl)diazirine photoincorporation. In the presence of phencyclidine, the subunit labeling pattern is distinct from that observed in either the resting or desensitized conformations; specifically, there is a concentration-dependent increase in the extent of photoincorporation into the delta-subunit. Our data show that domains of the nicotinic acetylcholine receptor interconvert between the resting and desensitized states independently of each other and suggest a revised model of channel blocker action that involves both low and high affinity agonist binding conformational intermediates.

PubMedSearch : Ryan_2001_J.Biol.Chem_276_4796
PubMedID: 11083863

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Citations formats

Ryan SE, Blanton MP, Baenziger JE (2001)
A conformational intermediate between the resting and desensitized states of the nicotinic acetylcholine receptor
Journal of Biological Chemistry 276 :4796

Ryan SE, Blanton MP, Baenziger JE (2001)
Journal of Biological Chemistry 276 :4796