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Molecular basis of ligand recognition and activation of the human succinate receptor SUCR1

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Fig. 1: Molecular mechanisms underlying ligand recognition and activation of SUCR1 receptor.

Data availability

The cryo-EM density maps and corresponding atomic coordinates for the SUCR1–Gi complexes bound to succinic acid, maleic acid, and compound 31 have been deposited in the Electron Microscopy Data Bank (EMDB) and the Protein Data Bank (PDB), respectively, with the following accession codes: EMD-39374 and 8YKW for the SUCR1–Gi complex bound to succinic acid; EMD-39375 and 8YKX for the SUCR1–Gi complex bound to maleic acid; EMD-39373 and 8YKV for the SUCR1–Gi complex bound to compound 31.

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Acknowledgements

This work was supported by grants from CAS Strategic Priority Research Program (XDB37030103 to H.E.X.); Shanghai Municipal Science and Technology Major Project (2019SHZDZX02 to H.E.X.); Shanghai Municipal Science and Technology Major Project (H.E.X.); the National Natural Science Foundation of China (32130022, 82121005); the Lingang Laboratory (LG-GG-202204-01 to H.E.X.); the National Key R&D Program of China (2022YFC2703105 to H.E.X.). The cryo-EM data were collected at the Shanghai Advanced Electron Microscope Center, Shanghai Institute of Material Medica, Chinese Academy of Sciences. We thank Qingning Yuan, Kai Wu, Wen Hu, Shuai Li and Shufeng Zhang at the Shanghai Advanced Electron Microscope Center, Shanghai Institute of Material Medica, for providing technical support and assistance during data collection.

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Contributions

H.E.X. initiated the project. C.L. designed and screened the expression constructs of SUCR1, prepared protein samples of succinic acid–SUCR1–Gi complex, maleic acid–SUCR1–Gi complex, and compound 31–SUCR1–Gi complex for cryo-EM data collection, participated in cryo-EM grid inspection, and executed the functional studies. H.L. performed cryo-EM grid preparation, data acquisition, structure determination and model building, and prepared the draft of the manuscript and figures. J.L. performed cell-based functional assay and participated in figure preparation. X.H. performed molecular dynamics simulations to validate ligand binding pose in SCUR1. H.Z. synthesized the compound 31 for structural study under the guidance of W.F. H.E.X. wrote the manuscript with input from all authors.

Corresponding authors

Correspondence to Wei Fu or H. Eric Xu.

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The authors declare no competing interests.

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Li, C., Liu, H., Li, J. et al. Molecular basis of ligand recognition and activation of the human succinate receptor SUCR1. Cell Res (2024). https://doi.org/10.1038/s41422-024-00984-7

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