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Structural insights into asymmetric activation of the calcium-sensing receptor–Gq complex

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Fig. 1: Cryo-EM structures of cinacalcet-bound CaSR and CaSR–Gq complex and asymmetric activation mechanism of CaSR.

Data availability

For CaSR–Gq complex and PAM-bound CaSR, the atomic coordinates have been deposited in the Protein Data Bank with accession codes 8WPU and 8WPG, and the EM maps have been deposited in the Electron Microscopy Database with accession codes EMD-37724 and EMD-37716.

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Acknowledgements

We thank the Cryo-EM Center at University of Science and Technology of China for the support of cryo-EM data collection. This work was funded by the National Natural Science Foundation of China (21825703 and 21927814 to C.T., 31971152 and 22277114 to P.S., 22307113 to S.L.), the National Key R&D Program of China (2021YFA1200104 to S.L., 2022YFC3400500 to C.T.), the Strategic Priority Research Program of Chinese Academy of Sciences (XDB37000000 to C.T.), and the Natural Science Foundation of Anhui Province (2108085J16 to P.S.).

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Author notes

  1. These authors contributed equally: Shenglong Ling, Xianyu Meng.

Authors and Affiliations

  1. Department of Endocrinology, Institute of Endocrine and Metabolic Disease, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Joint Center for Biological Analytical Chemistry, Anhui Engineering Laboratory of Peptide Drug, Anhui Laboratory of Advanced Photonic Science and Technology, University of Science and Technology of China, Hefei, Anhui, China

    Shenglong Ling, Xianyu Meng, Yuan Zhang, Zhemin Xia, Yingxin Zhou, Fan Yang, Pan Shi, Chaowei Shi & Changlin Tian

  2. The Anhui Provincial Key Laboratory of High Magnetic Resonance Image, High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui, China

    Changlin Tian

  3. Beijing Life Science Academy, Beijing, China

    Changlin Tian

  4. School of Biomedical Engineering, Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, Jiangsu, China

    Changlin Tian

Authors
  1. Shenglong Ling
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  2. Xianyu Meng
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Contributions

S.L. and X.M. prepared the samples, collected cryo-EM data, performed model building and structure refinements. X.M., Y.Z., Z.X., Y.X.Z. and F.Y. performed functional assays. P.S. and C.S. performed NMR analysis. C.T. and S.L. initiated and supervised the project, and wrote the manuscript with input from all authors.

Corresponding authors

Correspondence to Shenglong Ling, Pan Shi, Chaowei Shi or Changlin Tian.

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The authors declare no competing interests.

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Ling, S., Meng, X., Zhang, Y. et al. Structural insights into asymmetric activation of the calcium-sensing receptor–Gq complex. Cell Res 34, 169–172 (2024). https://doi.org/10.1038/s41422-023-00892-2

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