Abstract:
:The potassium channel selectivity filter both discriminates between K(+) and sodium ions and contributes to gating of ion flow. Static structures of conducting (open) and nonconducting (inactivated) conformations of this filter are known; however, the sequence of protein rearrangements that connect these two states is not. We show that closure of the selectivity filter gate in the human K(v)11.1 K(+) channel (also known as hERG, for ether-a-go-go-related gene), a key regulator of the rhythm of the heartbeat, is initiated by K(+) exit, followed in sequence by conformational rearrangements of the pore domain outer helix, extracellular turret region, voltage sensor domain, intracellular domains and pore domain inner helix. In contrast to the simple wave-like sequence of events proposed for opening of ligand-gated ion channels, a complex spatial and temporal sequence of widespread domain motions connect the open and inactivated states of the K(v)11.1 K(+) channel.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Wang DT,Hill AP,Mann SA,Tan PS,Vandenberg JIdoi
10.1038/nsmb.1966subject
Has Abstractpub_date
2011-01-01 00:00:00pages
35-41issue
1eissn
1545-9993issn
1545-9985pii
nsmb.1966journal_volume
18pub_type
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