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Interaction between residues in the Mg2+-binding site regulates BK channel activation.

Publication ,  Journal Article
Yang, J; Yang, H; Sun, X; Delaloye, K; Yang, X; Moller, A; Shi, J; Cui, J
Published in: J Gen Physiol
February 2013

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 conformational changes of the VSD induced by membrane voltage changes trigger the opening of the pore-gate domain. Although some structural information of these individual functional domains is available, how the interactions among these domains, especially the noncovalent interactions, control the dynamic gating process of BK channels is still not clear. Previous studies discovered that intracellular Mg(2+) binds to an interdomain binding site consisting of D99 and N172 from the membrane-spanning domain and E374 and E399 from the cytosolic domain. The bound Mg(2+) at this narrow interdomain interface activates the BK channel through an electrostatic interaction with a positively charged residue in the VSD. In this study, we investigated the potential interdomain interactions between the Mg(2+)-coordination residues and their effects on channel gating. By introducing different charges to these residues, we discovered a native interdomain interaction between D99 and E374 that can affect BK channel activation. To understand the underlying mechanism of the interdomain interactions between the Mg(2+)-coordination residues, we introduced artificial electrostatic interactions between residues 172 and 399 from two different domains. We found that the interdomain interactions between these two positions not only alter the local conformations near the Mg(2+)-binding site but also change distant conformations including the pore-gate domain, thereby affecting the voltage- and Ca(2+)-dependent activation of the BK channel. These results illustrate the importance of interdomain interactions to the allosteric gating mechanisms of BK channels.

Duke Scholars

Published In

J Gen Physiol

DOI

EISSN

1540-7748

Publication Date

February 2013

Volume

141

Issue

2

Start / End Page

217 / 228

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Physiology
  • Oocytes
  • Models, Biological
  • Membrane Potentials
  • Magnesium
  • Large-Conductance Calcium-Activated Potassium Channels
  • Ion Channel Gating
  • Computer Simulation
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
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Yang, J., Yang, H., Sun, X., Delaloye, K., Yang, X., Moller, A., … Cui, J. (2013). Interaction between residues in the Mg2+-binding site regulates BK channel activation. J Gen Physiol, 141(2), 217–228. https://doi.org/10.1085/jgp.201210794
Yang, Junqiu, Huanghe Yang, Xiaohui Sun, Kelli Delaloye, Xiao Yang, Alyssa Moller, Jingyi Shi, and Jianmin Cui. “Interaction between residues in the Mg2+-binding site regulates BK channel activation.J Gen Physiol 141, no. 2 (February 2013): 217–28. https://doi.org/10.1085/jgp.201210794.
Yang J, Yang H, Sun X, Delaloye K, Yang X, Moller A, et al. Interaction between residues in the Mg2+-binding site regulates BK channel activation. J Gen Physiol. 2013 Feb;141(2):217–28.
Yang, Junqiu, et al. “Interaction between residues in the Mg2+-binding site regulates BK channel activation.J Gen Physiol, vol. 141, no. 2, Feb. 2013, pp. 217–28. Pubmed, doi:10.1085/jgp.201210794.
Yang J, Yang H, Sun X, Delaloye K, Yang X, Moller A, Shi J, Cui J. Interaction between residues in the Mg2+-binding site regulates BK channel activation. J Gen Physiol. 2013 Feb;141(2):217–228.

Published In

J Gen Physiol

DOI

EISSN

1540-7748

Publication Date

February 2013

Volume

141

Issue

2

Start / End Page

217 / 228

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Physiology
  • Oocytes
  • Models, Biological
  • Membrane Potentials
  • Magnesium
  • Large-Conductance Calcium-Activated Potassium Channels
  • Ion Channel Gating
  • Computer Simulation
  • Cells, Cultured