Unknown

Dataset Information

0

Inverted allosteric coupling between activation and inactivation gates in K+ channels.


ABSTRACT: The selectivity filter and the activation gate in potassium channels are functionally and structurally coupled. An allosteric coupling underlies C-type inactivation coupled to activation gating in this ion-channel family (i.e., opening of the activation gate triggers the collapse of the channel's selectivity filter). We have identified the second Threonine residue within the TTVGYGD signature sequence of K+ channels as a crucial residue for this allosteric communication. A Threonine to Alanine substitution at this position was studied in three representative members of the K+-channel family. Interestingly, all of the mutant channels exhibited lack of C-type inactivation gating and an inversion of their allosteric coupling (i.e., closing of the activation gate collapses the channel's selectivity filter). A state-dependent crystallographic study of KcsA-T75A proves that, on activation, the selectivity filter transitions from a nonconductive and deep C-type inactivated conformation to a conductive one. Finally, we provide a crystallographic demonstration that closed-state inactivation can be achieved by the structural collapse of the channel's selectivity filter.

SUBMITTER: Labro AJ 

PROVIDER: S-EPMC6003467 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2016-01-01 | S-EPMC4922147 | BioStudies
2015-01-01 | S-EPMC4687598 | BioStudies
2020-01-01 | S-EPMC7231921 | BioStudies
2010-01-01 | S-EPMC2828906 | BioStudies
2019-01-01 | S-EPMC6879586 | BioStudies
2011-01-01 | S-EPMC3093550 | BioStudies
2010-01-01 | S-EPMC3033755 | BioStudies
2019-01-01 | S-EPMC6342527 | BioStudies
2018-01-01 | S-EPMC6168234 | BioStudies
2011-01-01 | S-EPMC3141920 | BioStudies