The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism

doi:10.1038/s41594-020-0439-z

. 2020 Jul;27(7):645-652.

doi: 10.1038/s41594-020-0439-z. Epub 2020 Jun 22.

The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism

Hiroto Shimada^#¹, Tsukasa Kusakizako^#¹, T H Dung Nguyen², Tomohiro Nishizawa¹, Tomoya Hino^{3

4}, Makoto Tominaga², Osamu Nureki⁵

Affiliations

¹ Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
² Division of Cell Signaling, National Institute for Physiological Sciences, National Institute of Natural Sciences, Okazaki, Japan.
³ Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori, Japan.
⁴ Center for Research on Green Sustainable Chemistry, Tottori University, Tottori, Japan.
⁵ Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. nureki@bs.s.u-tokyo.ac.jp.

^# Contributed equally.

PMID: 32572254
DOI: 10.1038/s41594-020-0439-z

The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism

Hiroto Shimada et al. Nat Struct Mol Biol. 2020 Jul.

. 2020 Jul;27(7):645-652.

doi: 10.1038/s41594-020-0439-z. Epub 2020 Jun 22.

Authors

Hiroto Shimada^#¹, Tsukasa Kusakizako^#¹, T H Dung Nguyen², Tomohiro Nishizawa¹, Tomoya Hino^{3

4}, Makoto Tominaga², Osamu Nureki⁵

Affiliations

¹ Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
² Division of Cell Signaling, National Institute for Physiological Sciences, National Institute of Natural Sciences, Okazaki, Japan.
³ Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori, Japan.
⁴ Center for Research on Green Sustainable Chemistry, Tottori University, Tottori, Japan.
⁵ Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. nureki@bs.s.u-tokyo.ac.jp.

^# Contributed equally.

PMID: 32572254
DOI: 10.1038/s41594-020-0439-z

Abstract

Transient receptor potential vanilloid subfamily member 3 (TRPV3) is a temperature-sensitive cation channel. Previous cryo-EM analyses of TRPV3 in detergent micelles or amphipol proposed that the lower gate opens by α-to-π helical transitions of the nearby S6 helix. However, it remains unclear how physiological lipids are involved in the TRPV3 activation. Here we determined the apo state structure of mouse (Mus musculus) TRPV3 in a lipid nanodisc at 3.3 Å resolution. The structure revealed that lipids bound to the pore domain stabilize the selectivity filter in the narrow state, suggesting that the selectivity filter of TRPV3 affects cation permeation. When the lower gate is closed in nanodisc-reconstituted TRPV3, the S6 helix adopts the π-helical conformation without agonist- or heat-sensitization, potentially stabilized by putative intra-subunit hydrogen bonds and lipid binding. Our findings provide insights into the lipid-associated gating mechanism of TRPV3.

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References

1. Ramsey, I. S., Delling, M. & Clapham, D. E. An introduction to Trp channels. Ann. Rev. Physiol. 68, 619–647 (2005). - DOI
1. Smith, G. D. et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418, 186–190 (2002). - PubMed - DOI
1. Xu, H. et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418, 181–186 (2002). - PubMed - DOI
1. Sherkheli, M. A., Vogt-Eisele, A. K., Weber, K. & Hatt, H. Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues. Pak. J. Pharm. Sci. 26, 431–438 (2013). - PubMed
1. Chung, M.-K. 2-Aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3. J. Neurosci. 24, 5177–5182 (2004). - PubMed - PMC - DOI

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[1] Ramsey, I. S., Delling, M. & Clapham, D. E. An introduction to Trp channels. Ann. Rev. Physiol. 68, 619–647 (2005). - DOI

[2] Ramsey, I. S., Delling, M. & Clapham, D. E. An introduction to Trp channels. Ann. Rev. Physiol. 68, 619–647 (2005). - DOI

[3] Smith, G. D. et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418, 186–190 (2002). - PubMed - DOI

[4] Smith, G. D. et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418, 186–190 (2002). - PubMed - DOI

[5] Xu, H. et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418, 181–186 (2002). - PubMed - DOI

[6] Xu, H. et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418, 181–186 (2002). - PubMed - DOI

[7] Sherkheli, M. A., Vogt-Eisele, A. K., Weber, K. & Hatt, H. Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues. Pak. J. Pharm. Sci. 26, 431–438 (2013). - PubMed

[8] Sherkheli, M. A., Vogt-Eisele, A. K., Weber, K. & Hatt, H. Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues. Pak. J. Pharm. Sci. 26, 431–438 (2013). - PubMed

[9] Chung, M.-K. 2-Aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3. J. Neurosci. 24, 5177–5182 (2004). - PubMed - PMC - DOI

[10] Chung, M.-K. 2-Aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3. J. Neurosci. 24, 5177–5182 (2004). - PubMed - PMC - DOI

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The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism

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The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism

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