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@ARTICLE{Kowal:153358,
author = {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},
title = {{L}igand-induced structural changes in the cyclic
nucleotide-modulated potassium channel {M}lo{K}1},
journal = {Nature Communications},
volume = {5},
issn = {2041-1723},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2014-02989},
pages = {(1-10) 4106},
year = {2014},
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.},
cin = {ICS-6},
ddc = {500},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {452 - Structural Biology (POF2-452)},
pid = {G:(DE-HGF)POF2-452},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000331084400015},
pubmed = {pmid:24469021},
doi = {10.1038/ncomms4106},
url = {https://juser.fz-juelich.de/record/153358},
}