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. 2023 Jun 3;14:3224. doi: 10.1038/s41467-023-38942-3

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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 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. 4 — a VPC and HDA are accommodated at the III-IV fenestration, and the elongated linear VXT projects into the central cavity from the IV-I fenestration. Two perpendicular views of the PD are shown. b Different binding poses at the fenestration sites. Shown here are cut-open electrostatic surfaces viewed from the extracellular side. The drugs are shown as spheres. c Details of VPC, HDA, and VXT coordination. d Different states of the IV-I fenestration in the presence of distinct pore blockers. The fenestration, which exists in the apo or VXT, HDA and VPC-bound channel, is gone in the presence of BPV, CBZ, or LCM accompanying the α→π transition of S6_IV.