Publication
Title
Inverted allosteric coupling between activation and inactivation gates in $K^{+}$ channels
Author
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.
Language
English
Source (journal)
Proceedings of the National Academy of Sciences of the United States of America. - Washington, D.C.
AMERICA
Publication
Washington, D.C. : 2018
ISSN
0027-8424 [Print]
1091-6490 [Online]
Volume/pages
115 :21 (2018) , p. 5426-5431
ISI
000432663000053
Pubmed ID
29735651
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
 Faculty/Department Research group Publication type Subject Affiliation Publications with a UAntwerp address