6by2

Publication Abstract from PubMed

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.

Inverted allosteric coupling between activation and inactivation gates in K(+) channels.,Labro AJ, Cortes DM, Tilegenova C, Cuello LG Proc Natl Acad Sci U S A. 2018 May 7. pii: 1800559115. doi:, 10.1073/pnas.1800559115. PMID:29735651^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.