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Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1

Kowal, Julia and Chami, Mohamed and Baumgartner, Paul and Arheit, Marcel and Chiu, Po-Lin and Rangl, Martina and Scheuring, Simon and Schröder, Gunnar F. and Nimigean, Crina M. and Stahlberg, Henning. (2014) Ligand-induced structural changes in the cyclic nucleotide-modulated potassium channel MloK1. Nature communications, Vol. 5 , Article Nr. 3106.

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Official URL: http://edoc.unibas.ch/dok/A6212013

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Abstract

Cyclic nucleotide-modulated ion channels are important for signal transduction and pacemaking in eukaryotes. The molecular determinants of ligand gating in these channels are still unknown, mainly because of a lack of direct structural information. Here we report ligand-induced conformational changes in full-length MloK1, a cyclic nucleotide-modulated potassium channel from the bacterium Mesorhizobium loti, analysed by electron crystallography and atomic force microscopy. Upon cAMP binding, the cyclic nucleotide-binding domains move vertically towards the membrane, and directly contact the S1-S4 voltage sensor domains. This is accompanied by a significant shift and tilt of the voltage sensor domain helices. In both states, the inner pore-lining helices are in an 'open' conformation. We propose a mechanism in which ligand binding can favour pore opening via a direct interaction between the cyclic nucleotide-binding domains and voltage sensors. This offers a simple mechanistic hypothesis for the coupling between ligand gating and voltage sensing in eukaryotic HCN channels.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing Group
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Jun 2014 07:56
Deposited On:31 Jan 2014 09:51

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