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. 2022 Feb 25;13:1057. doi: 10.1038/s41467-022-28683-0

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Structural comparison of tirzepatide–GIPR–G_s and tirzepatide–GLP-1R–G_s. Receptor ECD and G protein are omitted for clarity. b Interactions between tirzepatide (salmon) and the TMD of GIPR (yellow green). Residues involved in interactions are shown as sticks. c Interactions between tirzepatide (light salmon) and the TMD of GLP-1R (dodger blue). Residues involved in interactions are shown as sticks. d–e Effects of receptor mutations on tirzepatide-induced cAMP accumulation. Data shown are means ± S.E.M. of three independent experiments (n = 3) performed in quadruplicate. f The peptide recognition modes are described by fingerprint strings encoding different interaction types of the surrounding residues in each receptor. Residues that show no interaction with receptors are displayed as white circles. Color codes are listed on the top panel. WT, wild-type. Source data are provided as a Source Data file.