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. 2022 May 23;13:2855. doi: 10.1038/s41467-022-30595-y

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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 Detailed interactions between compound-110 (pink) and M4R (green) from the extracellular view. Residues involved in the binding pocket of M4R are mainly hydrophobic (green sticks) and are derived from TM2, TM6, TM7, and ECL3. b The BRET results of WT-M4R and mutants in coupling with G_i1. Values are shown as the mean ± SEM from n = 4 independent biological replicates, each biological replicate has two technical replicates. c The side view of the compound-110 (pink sphere) binding pose in M4R (green) with the key residues (cyan) related to activation. d The characterization of compound-110 in BRET assay. Source data are provided as a Source Data file.