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@ARTICLE{Sachyani:207416,
author = {Sachyani, Dana and Dvir, Meidan and Strulovich, Roi and
Tria, Giancarlo and Tobelaim, William and Peretz, Asher and
Pongs, Olaf and Svergun, Dmitri and Attali, Bernard and
Hirsch, Joel A.},
title = {{S}tructural {B}asis of a {K}v7.1 {P}otassium {C}hannel
{G}ating {M}odule: {S}tudies of the {I}ntracellular
{C}-{T}erminal {D}omain in {C}omplex with {C}almodulin},
journal = {Structure},
volume = {22},
number = {11},
issn = {0969-2126},
address = {London [u.a.]},
publisher = {Elsevier Science},
reportid = {PUBDB-2015-01326},
pages = {1582 - 1594},
year = {2014},
note = {(c) Elsevier Ltd.},
abstract = {Kv7 channels tune neuronal and cardiomyocyte excitability.
In addition to the channel membrane domain, they also have a
unique intracellular C-terminal (CT) domain, bound
constitutively to calmodulin (CaM). This CT domain regulates
gating and tetramerization. We investigated the structure of
the membrane proximal CT module in complex with CaM by X-ray
crystallography. The results show how the CaM intimately
hugs a two-helical bundle, explaining many channelopathic
mutations. Structure-based mutagenesis of this module in the
context of concatemeric tetramer channels and functional
analysis along with in vitro data lead us to propose that
one CaM binds to one individual protomer, without
crosslinking subunits and that this configuration is
required for proper channel expression and function.
Molecular modeling of the CT/CaM complex in conjunction with
small-angle X-ray scattering suggests that the membrane
proximal region, having a rigid lever arm, is a critical
gating regulator.},
cin = {EMBL / EMBL-User},
ddc = {570},
cid = {I:(DE-H253)EMBL-20120731 / I:(DE-H253)EMBL-User-20120814},
pnm = {DORIS Beamline D1.2 (POF2-54G13)},
pid = {G:(DE-H253)POF2-D1.2-20130405},
experiment = {EXP:(DE-H253)D-D1.2-20150101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000344934300006},
pubmed = {pmid:25441029},
doi = {10.1016/j.str.2014.07.016},
url = {https://bib-pubdb1.desy.de/record/207416},
}