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. 2023 Jun 7;618(7967):1085–1093. doi: 10.1038/s41586-023-06169-3

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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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 5 — (a) Four active class B1 GPCRs (green, PTH1R; white, GLP-1R; pink, glucagon receptor [GCGR]; purple, corticotropin releasing factor receptor 1 [CRF1R]) are superimposed onto inactive or inactive-like structures. (b) PTH-bound PTH1R and PCO371-bound PTH1R are superimposed onto the ePTH-bound inactive-like PTH1R structure (green, PTH-bound PTH1R; orange, PTH; violet, PCO371-bound PTH1R; magenta, PCO371; gray, ePTH-bound PTH1R). PCO371-bound PTH1R exhibited the moderate kink in TM6 (approximately 145°), whereas PTH-bound PTH1R exhibited the typical sharp kink in TM6 (approximately 90°). (c) TM6 angle consisting of the three Cα atoms of the I/M/V^6.39, G^6.50, and A/V/L^6.54 residues. (d) PCO371 directly stabilizes the intracellular half of TM6 in the outward conformation, which increases the volume in the inner cavity and activates the G_s protein.