PUBLICATION
Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel
- Authors
- Yuan, P., Leonetti, M.D., Hsiung, Y., MacKinnon, R.
- ID
- ZDB-PUB-230620-78
- Date
- 2011
- Source
- Nature 481: 949794-7 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Crystallography, X-Ray
- Cytoplasm/metabolism
- Hypertension/metabolism
- Conserved Sequence
- Asthma/metabolism
- Pliability
- Zebrafish
- Calcium/metabolism*
- Calcium/pharmacology
- Humans
- Models, Biological
- Ion Channel Gating*/drug effects
- Protein Structure, Tertiary
- Models, Molecular
- Electric Conductivity*
- Animals
- Large-Conductance Calcium-Activated Potassium Channels/chemistry*
- Large-Conductance Calcium-Activated Potassium Channels/metabolism*
- PubMed
- 22139424 Full text @ Nature
Citation
Yuan, P., Leonetti, M.D., Hsiung, Y., MacKinnon, R. (2011) Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel. Nature. 481:949794-7.
Abstract
High-conductance voltage- and Ca(2+)-activated K(+) channels function in many physiological processes that link cell membrane voltage and intracellular Ca(2+) concentration, including neuronal electrical activity, skeletal and smooth muscle contraction, and hair cell tuning. Like other voltage-dependent K(+) channels, Ca(2+)-activated K(+) channels open when the cell membrane depolarizes, but in contrast to other voltage-dependent K(+) channels, they also open when intracellular Ca(2+) concentrations rise. Channel opening by Ca(2+) is made possible by a structure called the gating ring, which is located in the cytoplasm. Recent structural studies have defined the Ca(2+)-free, closed, conformation of the gating ring, but the Ca(2+)-bound, open, conformation is not yet known. Here we present the Ca(2+)-bound conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca(2+), opens like the petals of a flower. The degree to which it opens explains how Ca(2+) binding can open the transmembrane pore. These findings present a molecular basis for Ca(2+) activation of K(+) channels and suggest new possibilities for targeting the gating ring to treat conditions such as asthma and hypertension.
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