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. 2023 Sep 25;8:364. doi: 10.1038/s41392-023-01625-y

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© The Author(s) 2023

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. 1 — Signal transduction and structure of MK-6892-HCAR2-G_i complex. a Downstream signals and functions mediated by HCAR2. The schematic figure created with BioRender.com. b Represented curve for niacin and MK-6892-induced HCAR2 activation examined by cAMP inhibition assay. c Activating effect of MK-6892 on HCARs by cAMP inhibition assay. Data are presented as the mean ± SEM of three independent experiments performed in triplicate. d The cryo-EM map (left panel) and structural mode (right panel) of MK-6892-bound to HCAR2 in complex with G_i heterotrimer and scFv16. Orange, MK-6892; Light steel blue, HCAR2; Tan, Gα_i; Sky blue, Gβ; Rosy brown, Gγ; Dark gray, scFv16. The EM density of HCAR2-G_i complex and MK-6892 was shown with the counter level of 0.62, 0.469 respectively