Initial steps of inactivation at the K+ channel selectivity filter

Thomson, Andrew S. and Heer, Florian T. and Smith, Frank J. and Hendron, Eunan and Bernèche, Simon and Rothberg, Brad S.. (2014) Initial steps of inactivation at the K+ channel selectivity filter. Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, H. 17 , E1713-E1722.

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Official URL: http://edoc.unibas.ch/dok/A6263086

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K(+) efflux through K(+) channels can be controlled by C-type inactivation, which is thought to arise from a conformational change near the channel's selectivity filter. Inactivation is modulated by ion binding near the selectivity filter; however, the molecular forces that initiate inactivation remain unclear. We probe these driving forces by electrophysiology and molecular simulation of MthK, a prototypical K(+) channel. Either Mg(2+) or Ca(2+) can reduce K(+) efflux through MthK channels. However, Ca(2+), but not Mg(2+), can enhance entry to the inactivated state. Molecular simulations illustrate that, in the MthK pore, Ca(2+) ions can partially dehydrate, enabling selective accessibility of Ca(2+) to a site at the entry to the selectivity filter. Ca(2+) binding at the site interacts with K(+) ions in the selectivity filter, facilitating a conformational change within the filter and subsequent inactivation. These results support an ionic mechanism that precedes changes in channel conformation to initiate inactivation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Computational Biophysics (Bernèche)
UniBasel Contributors:Bernèche, Simon and Heer, Florian
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Jun 2014 07:56
Deposited On:20 Jun 2014 07:56

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