Interaction between residues in the Mg-binding site regulates BK channel activation
نویسندگان
چکیده
The large conductance, voltageand Ca-activated K (BK) channel plays important roles in many physiological processes, such as muscle contraction, neural transmission, and circadian pacemaker output (Brayden and Nelson, 1992; Robitaille et al., 1993; Meredith et al., 2006). A functional BK channel is composed of four Slo1 subunits, each of which comprises multiple structural modules (Fig. 1, A and B): a membrane-spanning domain including the pore-gate (S5 and S6) and voltage-sensing domain (VSD; S1 to S4), and a large cytosolic domain that contains two Ca-binding sites to serve as the Ca sensor (Adelman et al., 1992; Schreiber and Salkoff, 1997; Xia et al., 2002; Zhang et al., 2010). Conformational changes of the VSD upon membrane depolarization and conformational changes of the cytosolic domain upon Ca binding control BK channel activation.
منابع مشابه
Interaction between residues in the Mg2+-binding site regulates BK channel activation
As a unique member of the voltage-gated potassium channel family, a large conductance, voltage- and Ca(2+)-activated K(+) (BK) channel has a large cytosolic domain that serves as the Ca(2+) sensor, in addition to a membrane-spanning domain that contains the voltage-sensing (VSD) and pore-gate domains. The conformational changes of the cytosolic domain induced by Ca(2+) binding and the conformat...
متن کاملHeme is a carbon monoxide receptor for large-conductance Ca2+-activated K+ channels.
Carbon monoxide (CO) is an endogenous paracrine and autocrine gaseous messenger that regulates physiological functions in a wide variety of tissues. CO induces vasodilation by activating arterial smooth muscle large-conductance Ca2+-activated potassium (BK(Ca)) channels. However, the mechanism by which CO activates BK(Ca) channels remains unclear. Here, we tested the hypothesis that CO activate...
متن کاملNonselective, Low Affinity Divalent Cation Site
The ability of membrane voltage to activate high conductance, calcium-activated (BK-type) K channels is enhanced by cytosolic calcium (Ca 2 ). Activation is sensitive to a range of [Ca 2 ] that spans over four orders of magnitude. Here, we examine the activation of BK channels resulting from expression of cloned mouse Slo1 subunits at [Ca 2 ] and [Mg 2 ] up to 100 mM. The half-activation voltag...
متن کاملTuning magnesium sensitivity of BK channels by mutations.
Intracellular Mg(2+) at physiological concentrations activates mSlo1 BK channels by binding to a metal-binding site in the cytosolic domain. Previous studies suggest that residues E374, Q397, and E399 are important in Mg(2+) binding. In the present study, we show that mutations of E374 or E399 to other amino acids, except for Asp, abolish Mg(2+) sensitivity. These results further support that t...
متن کاملExploring the Interaction Mechanism of Coumarin with Bovine β-Casein: Spectrofluorometric and Molecular Modeling Studies
This paper is designed to examine the binding behavior of Coumarin with bovine -casein (βCN) through fluorescence spectroscopy and molecular modeling techniques. The data analysis on fluorescence titration experiments at various temperatures represents the enthalpy driven nature for the formation of Coumarin–βCN complex and the prevailed role of hydrogen bonds and van der Waals interactions in...
متن کامل