Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 27562Article in journal (Refereed) PublishedText
Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel.
Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2016. Vol. 6, 27562
IdentifiersURN: urn:nbn:se:liu:diva-130064DOI: 10.1038/srep27562ISI: 000377343800001PubMedID: 27278891OAI: oai:DiVA.org:liu-130064DiVA: diva2:947007
Funding Agencies|Swedish Research Council; Swedish Brain Foundation; Swedish Heart-Lung Foundation; Swedish e-Science Research Center; Foundation Blanceflor Boncompagni Ludovisi, nee Bildt2016-07-062016-07-062016-07-27