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Title
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Inverted allosteric coupling between activation and inactivation gates in channels
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Proceedings of the National Academy of Sciences of the United States of America. - Washington, D.C.
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AMERICA
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Publication
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Washington, D.C.
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2018
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ISSN
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0027-8424
[Print]
1091-6490
[Online]
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DOI
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10.1073/PNAS.1800559115
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Volume/pages
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115
:21
(2018)
, p. 5426-5431
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ISI
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000432663000053
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Pubmed ID
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29735651
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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