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BRIEF RESEARCH REPORT article
Front. Mol. Biosci.
Sec. Structural Biology
Volume 11 - 2024 |
doi: 10.3389/fmolb.2024.1454273
Structural bases for blockade and activation of BK channels by Ba 2+ ions
Provisionally accepted- 1 National Institute of Neurological Disorders and Stroke (NIH), Bethesda, United States
- 2 Institute of Biomedical Technologies, Faculty of Health Sciences, University of La Laguna, Tenerife, Spain
- 3 National Institute of Allergy and Infectious Diseases (NIH), Bethesda, Maryland, United States
We studied the impact of Ba2+ ions on the function and structure of large conductance potassium (BK) channels. Ion composition has played a crucial role in the physiological studies of BK channels due to their ability to couple ion composition and membrane voltage signaling. Unlike Ca2+, which activates BK channels through all Regulator of K+ Conductance (RCK) domains, Ba 2+ has been described as specifically interacting with the RCK2 domain. It has been shown that Ba2+ also blocks potassium permeation by binding to the channel's selectivity filter. The Cryo-EM structure of the Aplysia BK channel in the presence of high concentration Ba2+ here presented (PDBID: 7RJT) revealed that Ba2+ occupies the K+ S3 site in the selectivity filter. Densities attributed to K+ ions were observed at sites S2 and S4. Ba2+ ions were also found bound to the high-affinity Ca2+ binding sites RCK1 and RCK2, which agrees with functional work suggesting that the Ba2+ increases open probability through the Ca2+ bowl site (RCK2). A comparative analysis with a second structure here presented (PDBID: 7RK6), obtained without additional Ba2+, shows localized changes between the RCK1 and RCK2 domains, suggestive of coordinated dynamics between the RCK ion binding sites with possible relevance for the activation/blockade of the channel. The observed densities attributed to Ba2+ at RCK1 and RCK2 sites and the selectivity filter contribute to a deeper understanding of the structural basis for Ba2+ 's dual role in BK channel modulation, adding to the existing knowledge in this field.
Keywords: membrane, voltage, Divalent, Binding site, RCK domain
Received: 24 Jun 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Holmgren, Srivastava, Miranda, Giraldez, Zhu and Cachau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Miguel Holmgren, National Institute of Neurological Disorders and Stroke (NIH), Bethesda, United States
Shubhra Srivastava, National Institute of Neurological Disorders and Stroke (NIH), Bethesda, United States
Pablo Miranda, National Institute of Neurological Disorders and Stroke (NIH), Bethesda, United States
Jianghai Zhu, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, MD 20892-9807, Maryland, United States
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