Regulator of K + conductance (RCK) domains control the activity of a variety of K + transporters and channels, including the human large conductance Ca 2+-activated K + channel that is important for blood pressure regulation and control of neuronal firing, and MthK, a prokaryotic Ca 2+-gated K + channel that has yielded structural insight toward mechanisms of RCK domain-controlled channel gating. In MthK, a gating ring of eight RCK domains regulates channel activation by Ca 2+. Here, using electrophysiology and X-ray crystallography, we show that each RCK domain contributes to three different regulatory Ca 2+-binding sites, two of which are located at the interfaces between adjacent RCK domains. The additional Ca 2+-binding sites, resulting in a stoichiometry of 24 Ca 2+ ions per channel, is consistent with the steep relation between [Ca 2+] and MthK channel activity. Comparison of Ca 2+-bound and unliganded RCK domains suggests a physical mechanism for Ca 2+-dependent conformational changes that underlie gating in this class of channels.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Oct 25 2011|
- Lipid bilayer
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