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Structural insights into the activation of GLP-1R by a small molecule agonist

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Fig. 1: Structure of RGT1383–GLP-1R–Gs complex.

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Acknowledgements

The cryo-EM data were collected at Cryo-Electron Microscopy Research Center, Shanghai Institute of Material Medica. This work was partially supported by the Ministry of Science and Technology (China) grants (2018YFA0507002 to H.E.X.); Shanghai Municipal Science and Technology Major Project (2019SHZDZX02 to H.E.X.); CAS Strategic Priority Research Program (XDB08020303 to H.E.X.); Shanghai Science and Technology Committee (19ZR1467500 to H.M.); the Young Innovator Association of CAS (H.M.); SA-SIBS Scholarship Program (L.Z.), the Young Innovator Association of CAS (2018325 to L.Z.); the National Natural Science Foundation of China (31770796 to Y.J.); the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” (2018ZX09711002 to Y.J.); the K.C. Wong Education Foundation (Y.J.).

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Contributions

H.M. carried out construct preparation, protein expression and purification and prepared the cryo-EM sample. H.M. and D.Y. collected the data. D.Y. processed cryo-EM data, modeled, refined and analyzed the structure, wrote manuscript with input from all authors. W.H. performed molecular docking. L.Z. designed the expression constructs for the compound–GLP-1R–Gs complex. X.W. purified the Nb35 nanobody and performed specimen screening by negative-stain EM. Y.J. assisted in construct preparation, protein expression, and purification. F.L. oversaw cell experiments. W.G. and X.S. assisted with model building. H.E.X. and W.Z. conceived of the project, W.Z. designed RGT1383, and H.E.X. supervised the overall structural studies and participated in manuscript writing.

Corresponding authors

Correspondence to Daopeng Yuan or H. Eric Xu.

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The authors declare no competing interests.

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Ma, H., Huang, W., Wang, X. et al. Structural insights into the activation of GLP-1R by a small molecule agonist. Cell Res 30, 1140–1142 (2020). https://doi.org/10.1038/s41422-020-0384-8

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