The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action
Open accessAbstract
When integral membrane proteins are visualized in detergents or other artificial systems, an important layer of information is lost regarding lipid interactions and their effects on protein structure. This is especially relevant to proteins for which lipids have both structural and regulatory roles. Here we demonstrate the power of combining electron cryo-microscopy with lipid nanodisc technology to ascertain the structure of the rat TRPV1 ion channel in a native bilayer environment. Using this approach, we determined the locations of annular and regulatory lipids and showed that specific phospholipid interactions enhance binding of a spider toxin to TRPV1 through formation of a tripartite complex. Furthermore, phosphatidylinositol lipids occupy the binding site for capsaicin and other vanilloid ligands, suggesting a mechanism whereby chemical or thermal stimuli elicit channel activation by promoting the release of bioactive lipids from a critical allosteric regulatory site. Cryo-electron microscopy has undergone a resolution revolution—here, this method has been combined with lipid nanodisc technology to solve structures of TRPV1, the receptor for capsaicin, in a membrane bilayer, revealing mechanisms of lipid and ligand regulation. Transient receptor potential (TRP) channels act as sensors for a wide range of physical and chemical stimuli. Here David Julius and colleagues combine electron cryo-microscopy with lipid nanodisc technology to solve structures of TRPV1, the receptor for capsaicin, in a membrane bilayer. The results reveal the mechanisms of lipid and ligand regulation. This approach, in which purified TRPV1 protein is reconstituted into lipid nanodiscs, provides a more native environment than the detergents or amphipols often used to stabilize target molecules, and may facilitate the three-dimensional structural analysis of other complex membrane proteins.
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PHENIX : a comprehensive Python-based system for macromolecular structure solution
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MolProbity : all-atom structure validation for macromolecular crystallography
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Cryo-EM structure of the ribosome-SecYE complex in the membrane environment.
Frauenfeld, J., Gumbart, J., Sluis, E. O. V. D., Funes, S., Gartmann, M., Beatrix, B., Mielke, T., Berninghausen, O., Becker, T., Schulten, K., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2026 · Cited by 298
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Self-citationMuller, M. P., Jiang, T., Sun, C., Lihan, M., Pant, S., Mahinthichaichan, P., Trifan, A., & Tajkhorshid, E. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00608 · Cited by 282
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Tapial Martínez, P., López Navajas, P., & Lietha, D. (2020) · Biomolecules · doi:10.3390/biom10020179 · Cited by 206
“Regarding membrane systems, nanodiscs have proven a suitable system for high resolution cryo-EM studies [91].”
Garami, A., Shimansky, Y. P., Rumbus, Z., Vizin, R. C. L., Farkas, N., Hegyi, J., Szakacs, Z., Solymar, M., Csenkey, A., Chiche, D. A., et al. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107474 · Cited by 159
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Fusion protein strategies for cryo-EM study of G protein-coupled receptors
Zhang, K., Wu, H., Hoppe, N., Manglik, A., & Cheng, Y. (2022) · Nature Communications · doi:10.1038/s41467-022-32125-2 · Cited by 91
Self-citationAyoubi‐Joshaghani, M. H., Dianat‐Moghadam, H., Seidi, K., Jahanban‐Esfahalan, A., Zare, P., & Jahanban‐Esfahlan, R. (2020) · Biotechnology and Bioengineering · doi:10.1002/bit.27248 · Cited by 52
Å.Nilsson, J. L., Mallet, C., Shionoya, K., Blomgren, A., Sundin, A. P., Grundemar, L., Boudieu, L., Blomqvist, A., Eschalier, A., Nilsson, U. J., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113042 · Cited by 17
Chen, M. (2025) · Communications Biology · doi:10.1038/s42003-025-08202-9 · Cited by 11
Metadata
- Authors
- Gao, Y., Cao, E., Julius, D., & Cheng, Y.
- Venue
- Nature
- Published
- 2016-05-18
- Volume
- 534
- Issue
- 7607
- Pages
- 347-351
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2404622021
- Cited by
- 814
- References
- 3
- FWCI
- 77.71
- Type
- journal article
- Language
- en
- Open access
- green
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