Shifts in the selectivity filter dynamics cause modal gating in K+ channels View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Shehrazade Jekhmane, João Medeiros-Silva, Jing Li, Felix Kümmerer, Christoph Müller-Hermes, Marc Baldus, Benoît Roux, Markus Weingarth

ABSTRACT

Spontaneous activity shifts at constant experimental conditions represent a widespread regulatory mechanism in ion channels. The molecular origins of these modal gating shifts are poorly understood. In the K+ channel KcsA, a multitude of fast activity shifts that emulate the native modal gating behaviour can be triggered by point-mutations in the hydrogen bonding network that controls the selectivity filter. Using solid-state NMR and molecular dynamics simulations in a variety of KcsA mutants, here we show that modal gating shifts in K+ channels are associated with important changes in the channel dynamics that strongly perturb the selectivity filter equilibrium conformation. Furthermore, our study reveals a drastically different motional and conformational selectivity filter landscape in a mutant that mimics voltage-gated K+ channels, which provides a foundation for an improved understanding of eukaryotic K+ channels. Altogether, our results provide a high-resolution perspective on some of the complex functional behaviour of K+ channels. More... »

PAGES

123

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-07973-6

    DOI

    http://dx.doi.org/10.1038/s41467-018-07973-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111164765

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30631074


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