Tuning magnesium sensitivity of BK channels by mutations.
Journal Article (Journal Article)
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 the side chains of E374 and E399 are essential for Mg(2+) coordination. To the contrary, none of the Q397 mutations abolishes Mg(2+) sensitivity, suggesting that its side chain may not coordinate to Mg(2+). However, because Q397 is spatially close to E374 and E399, its mutations affect the Mg(2+) sensitivity of channel gating by either reducing or increasing the Mg(2+) binding affinity. The pattern of mutational effects and the effect of chemical modification of Q397C indicate that Q397 is involved in the Mg(2+)-dependent activation of BK channels and that mutations of Q397 alter Mg(2+) sensitivity by affecting the conformation of the Mg(2+) binding site as well as by electrostatic interactions with the bound Mg(2+) ion.
Full Text
Duke Authors
Cited Authors
- Yang, H; Hu, L; Shi, J; Cui, J
Published Date
- October 15, 2006
Published In
Volume / Issue
- 91 / 8
Start / End Page
- 2892 - 2900
PubMed ID
- 16877509
Pubmed Central ID
- PMC1578465
International Standard Serial Number (ISSN)
- 0006-3495
Digital Object Identifier (DOI)
- 10.1529/biophysj.106.090159
Language
- eng
Conference Location
- United States