PubMed 20624858

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: BK , Slo1

Title: The RCK1 domain of the human BKCa channel transduces Ca2+ binding into structural rearrangements.

Authors: Taleh Yusifov, Anoosh D Javaherian, Antonios Pantazis, Chris S Gandhi, Riccardo Olcese

Journal, date & volume: J. Gen. Physiol., 2010 Aug , 136, 189-202

PubMed link:

Large-conductance voltage- and Ca(2+)-activated K(+) (BK(Ca)) channels play a fundamental role in cellular function by integrating information from their voltage and Ca(2+) sensors to control membrane potential and Ca(2+) homeostasis. The molecular mechanism of Ca(2+)-dependent regulation of BK(Ca) channels is unknown, but likely relies on the operation of two cytosolic domains, regulator of K(+) conductance (RCK)1 and RCK2. Using solution-based investigations, we demonstrate that the purified BK(Ca) RCK1 domain adopts an alpha/beta fold, binds Ca(2+), and assembles into an octameric superstructure similar to prokaryotic RCK domains. Results from steady-state and time-resolved spectroscopy reveal Ca(2+)-induced conformational changes in physiologically relevant [Ca(2+)]. The neutralization of residues known to be involved in high-affinity Ca(2+) sensing (D362 and D367) prevented Ca(2+)-induced structural transitions in RCK1 but did not abolish Ca(2+) binding. We provide evidence that the RCK1 domain is a high-affinity Ca(2+) sensor that transduces Ca(2+) binding into structural rearrangements, likely representing elementary steps in the Ca(2+)-dependent activation of human BK(Ca) channels.