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. 2021 Nov 4;12:6410. doi: 10.1038/s41467-021-26735-5

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© The Author(s) 2021

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. 2 — a Ghrelin binding in the cavity I and II. Ghrelin residues are labeled in orange. GHSR is colored in slate. b Binding of the octanoyl group of ghrelin in the cavity II. c Dose-dependent action of ghrelin on the wild type GHSR (wtGHSR) and mutants. d Alignment of ghrelin and ibutamoren. GHSR bound to ibutamoren is colored green. Ibutamoren is shown as yellow sticks. e Ibutamoren binding pocket. f Dose-dependent action of ibutamoren on wtGHSR and mutants. In c and f, agonist-induced GHSR signaling was measured by Ca²⁺ mobilization assay. Each data point represents mean ± S.D. from three independent assays. Polar interactions are shown as dashed lines in (a, b, and e).