Shaker-IR K+ channel gating in heavy water: Role of structural water molecules in inactivation.

ABSTRACT: It has been reported earlier that the slow (C-type) inactivated conformation in Kv channels is stabilized by a multipoint hydrogen-bond network behind the selectivity filter. Furthermore, MD simulations revealed that structural water molecules are also involved in the formation of this network locking the selectivity filter in its inactive conformation. We found that the application of an extracellular, but not intracellular, solution based on heavy water (D2O) dramatically slowed entry into the slow inactivated state in Shaker-IR mutants (T449A, T449A/I470A, and T449K/I470C, displaying a wide range of inactivation kinetics), consistent with the proposed effect of the dynamics of structural water molecules on the conformational stability of the selectivity filter. Alternative hypotheses ca

SUBMITTER: Szanto TG 

PROVIDER: S-EPMC8148028 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature