Unknown

Dataset Information

0

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.

SUBMITTER: daCosta CJ 

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

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3920732 | BioStudies
2018-01-01 | S-EPMC6036215 | BioStudies
2011-01-01 | S-EPMC3160419 | BioStudies
2013-01-01 | S-EPMC3912756 | BioStudies
2015-01-01 | S-EPMC4508619 | BioStudies
2018-01-01 | S-EPMC5940249 | BioStudies
2016-01-01 | S-EPMC5555364 | BioStudies
2014-01-01 | S-EPMC4072853 | BioStudies
2005-01-01 | S-EPMC2597414 | BioStudies
2012-01-01 | S-EPMC3420157 | BioStudies