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PDBsum entry 4umo
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Signaling protein
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PDB id
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4umo
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References listed in PDB file
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Key reference
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Title
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Structural basis of a kv7.1 potassium channel gating module: studies of the intracellular c-Terminal domain in complex with calmodulin.
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Authors
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D.Sachyani,
M.Dvir,
R.Strulovich,
G.Tria,
W.Tobelaim,
A.Peretz,
O.Pongs,
D.Svergun,
B.Attali,
J.A.Hirsch.
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Ref.
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Structure, 2014,
22,
1582-1594.
[DOI no: ]
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PubMed id
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Abstract
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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.
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