Dataset Information


Stoichiometry for ?-bungarotoxin block of ?7 acetylcholine receptors.

ABSTRACT: ?-Bungarotoxin (?-Btx) binds to the five agonist binding sites on the homopentameric ?7-acetylcholine receptor, yet the number of bound ?-Btx molecules required to prevent agonist-induced channel opening remains unknown. To determine the stoichiometry for ?-Btx blockade, we generate receptors comprised of wild-type and ?-Btx-resistant subunits, tag one of the subunit types with conductance mutations to report subunit stoichiometry, and following incubation with ?-Btx, monitor opening of individual receptor channels with defined subunit stoichiometry. We find that a single ?-Btx-sensitive subunit confers nearly maximal suppression of channel opening, despite four binding sites remaining unoccupied by ?-Btx and accessible to the agonist. Given structural evidence that ?-Btx locks the agonist binding site in an inactive conformation, we conclude that the dominant mechanism of antagonism is non-competitive, originating from conformational arrest of the binding sites, and that the five ?7 subunits are interdependent and maintain conformational symmetry in the open channel state.


PROVIDER: S-EPMC4544739 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

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