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. 2025 Jan 3;16:362. doi: 10.1038/s41467-024-55431-3

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© The Author(s) 2025

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/.

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Fig. 6 — a Front view of the transmembrane region of the LGR4-RSPO2-ZNRF3 in the different states aligned by the LGR4 TMD. The dashed line (violet/orange) indicates the position of ZNRF3 TM helices in the previous state. TM helix(a) is not visible in pentamer A, and the dashed line is colored in gray. For clarity, one LGR4 is omitted from the di-heterotrimer. b Cartoon illustrates the assembly pathway from the LGR4-apo state, and RSPO2-bound state, through LGR4-RSPO2-ZNRF3 (1:1:1, heterotrimer) state to LGR4-RSPO2-ZNRF3 (1:2:2, pentamer A) state, and then differentiates into the LGR4-RSPO2-ZNRF3 (1:2:2, pentamer B) state in the absence of LGR4, or into the LGR4-RSPO2-ZNRF3 (2:2:2, di-heterotrimer) state in the presence of LGR4.