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. 2022 Jan 4;12:798102. doi: 10.3389/fphys.2021.798102

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Copyright © 2022 Cheng, Arcario and Petroff.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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PIP₂ binding sites in TRP channels. (A) TRPV5 with PIP₂ (pdb 6dmu) and TRPV5 without PIP₂ (pdb 5irx). R302 and R384 are predicted to interact with the PIP₂ headgroup. Binding of PIP₂ is associated with outward movement of the S4-S5 linker and S6 away from the pore axis. (B) TRPM8 with PIP₂ and icilin (pdb 6nr3) and TRPM8 with low occupancy icilin (pdb 6nr4). K605, R850, and R997 are predicted to interact with the PIP₂ headgroup. Binding of the agonist icilin with high occupancy (not shown in this image) is associated with tilting of the TRP domain and movement of S4 (S4b) and S5, which brings R850 and R997 near the PIP₂ headgroup.