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

The Journal of General Physiology
Taleh YusifovRiccardo Olcese

Abstract

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.

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Citations

May 5, 2012·The Journal of Biological Chemistry·Nicoletta SavalliRiccardo Olcese
Nov 17, 2010·The Journal of General Physiology·Antonios PantazisRiccardo Olcese
Dec 20, 2012·The Journal of General Physiology·Sandipan Chowdhury, Baron Chanda
Jan 20, 2016·Molecular and Cellular Neurosciences·Francesca RizzoAlessandro Weisz
Jul 26, 2011·The European Journal of Neuroscience·Josef ButtigiegMichael G Fehlings
Jun 15, 2016·Annual Review of Biophysics·Ignacio Diaz-FranulicRamón Latorre
Apr 6, 2017·The Journal of Biological Chemistry·Yanyan GengCelia M Santi
May 3, 2013·Physiology·T HoshiR Olcese
Oct 13, 2016·The Biochemical Journal·Anna KicinskaPiotr Bednarczyk
Nov 4, 2016·Physiological Reviews·Ramon LatorreOsvaldo Alvarez
Mar 2, 2017·The Journal of General Physiology·Teresa Giraldez, Brad S Rothberg
Apr 2, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Piotr BednarczykAdam Szewczyk
Aug 15, 2018·Frontiers in Molecular Neuroscience·Aravind S KshatriTeresa Giraldez
May 7, 2021·Channels·Ana L González-CotaEnrique Balderas

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Methods Mentioned

BETA
light scattering
X-ray
size-exclusion chromatography
light-scattering
fluorescence spectroscopy

Software Mentioned

HORIBA
DSSP
MALLS
CDPro
DAS6
Astra
ImageJ

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