Abstract:
:The voltage-sensor domain (VSD) of voltage-dependent ion channels and enzymes is critical for cellular responses to membrane potential. The VSD can also be regulated by interaction with intracellular proteins and ligands, but how this occurs is poorly understood. Here, we show that the VSD of the BK-type K(+) channel is regulated by a state-dependent interaction with its own tethered cytosolic domain that depends on both intracellular Mg(2+) and the open state of the channel pore. Mg(2+) bound to the cytosolic RCK1 domain enhances VSD activation by electrostatic interaction with Arg-213 in transmembrane segment S4. Our results demonstrate that a cytosolic domain can come close enough to the VSD to regulate its activity electrostatically, thereby elucidating a mechanism of Mg(2+)-dependent activation in BK channels and suggesting a general pathway by which intracellular factors can modulate the function of voltage-dependent proteins.
journal_name
Proc Natl Acad Sci U S Aauthors
Yang H,Hu L,Shi J,Delaloye K,Horrigan FT,Cui Jdoi
10.1073/pnas.0705873104subject
Has Abstractpub_date
2007-11-13 00:00:00pages
18270-5issue
46eissn
0027-8424issn
1091-6490pii
0705873104journal_volume
104pub_type
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