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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. 4 — a Schematic summarizing the key translational and rotational movements contributing to M4R activation induced by compound-110. b Extracellular conformational changes from inactive (blue) to compound-110-bound active (green) M4R. c A specific ‘triangle frame’ formed by the side chains of residues Asp112^3.32, Ser85^2.57, and Tyr443^7.43 in the M4R–c110–G_i structure. d Conformational changes of residues Tyr416^6.51and Trp413^6.48 during M4R activation by compound-110. e Conformational changes of the NPxxY motif between inactive and compound-110-bound active M4R structures.