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Structural basis for different ω-agatoxin IVA sensitivities of the P-type and Q-type Cav2.1 channels

Cell Research (2024)Cite this article

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Dear Editor,

Voltage-gated calcium (Cav) channels are essential for mediating Ca2+ influx in response to membrane depolarization. Activation of Cav channels triggers fundamental physiological processes such as muscle contraction, neurotransmitter release, hormone secretion, and synaptic integration.1,2 The P/Q-type Cav channels Cav2.1, encoded by CACNA1A and prevalently found in neurons and neuroendocrine cells, play a vital role in the release of neurotransmitters and the regulation of synaptic plasticity and neuronal excitability.3 Cav2.1 presents a potential therapeutic target for treating neurological disorders, such as epilepsy and migraine.4

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Fig. 1: Structural basis for subtype-selective inhibition of Cav2.1 by Aga-IVA and MVIIC.

Data availability

The atomic coordinates of Cav2.1 in apo or in complex with toxins have been deposited in the Protein Data Bank (http://www.rcsb.org) under the accession codes 8X90 (Cav2.1-apo), 8X91 (Cav2.1-M) and 8X93 (Cav2.1-A). The corresponding cryo-EM maps have been deposited in the Electron Microscopy Data Bank (http://www.ebi.ac.uk/pdbe/emdb/) with the accession codes EMD-38158, EMD-38159 and EMD-38160, respectively.

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Acknowledgements

We thank Xiaomin Li and Jianlin Lei for technical support during EM image acquisition. We thank the Tsinghua University Branch of China National Center for Protein Sciences (Beijing) for providing the cryo-EM facility support. We thank the computational facility support on the cluster of Bio-Computing Platform (Tsinghua University Branch of China National Center for Protein Sciences Beijing). This work was funded by the National Natural Science Foundation of China (32330052).

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Author notes

  1. These authors contributed equally: Zhangqiang Li, Ye Cong, Tong Wu, Tongtong Wang.

Authors and Affiliations

  1. Beijing Frontier Research Center for Biological Structures, State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

    Zhangqiang Li, Ye Cong, Tong Wu, Tongtong Wang, Xinyao Lou, Xinyu Yang & Nieng Yan

  2. Institute of Bio-Architecture and Bio-Interactions, Shenzhen Medical Academy of Research and Translation, Shenzhen, Guangdong, China

    Nieng Yan

Authors
  1. Zhangqiang Li
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  2. Ye Cong
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Contributions

N.Y. conceived the project. Z.L., Y.C., T. Wang, X.L., and X.Y. performed structural determination. T. Wu performed and analyzed electrophysiological measurements. All authors contributed to data analysis. N.Y., Z.L., and T. Wang wrote the manuscript.

Corresponding authors

Correspondence to Zhangqiang Li or Nieng Yan.

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The authors declare no competing interests.

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Li, Z., Cong, Y., Wu, T. et al. Structural basis for different ω-agatoxin IVA sensitivities of the P-type and Q-type Cav2.1 channels. Cell Res (2024). https://doi.org/10.1038/s41422-024-00940-5

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