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. 2024 May 2;31(9):1377–1385. doi: 10.1038/s41594-024-01299-2

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© The Author(s) 2024

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. 4 — (a) Top: Top-down view of diC8-PIP₂ (green sticks and balls) and surrounding helices. Grey ghost tubes are TRPV1 bound with diC8-PIP₂ in the closed state and green tubes are in the dilated state. Bottom: schematic comparing the helical positions between the closed and dilated states. Pink triangles indicate the steric overlap between the diC8-PIP₂ molecule in the dilated state and the transmembrane helices of TRPV1 in the closed state. (b) Comparisons of the dilated state of TRPV1 with diC8-PIP₂ bound and other states. (c) Densities for cholesterol and a lipid (modeled as DOPC) that is found in a cleft between the S6 and S5 helices of adjacent monomers (see Fig. 3). (d) Interatom distances between two opposite cholesterol molecules demonstrating the pore radius formed by cholesterol. (e) Extra densities within the pore that are modeled as ordered water molecules due to the hydrophobic effect. 3 of the 4 cholesterol molecules are shown for clarity.