5IS0

Structure of TRPV1 in complex with capsazepine, determined in lipid nanodisc

Summary for 5IS0

• Entry DOI: 10.2210/pdb5is0/pdb
• Related: 5IRX 5IRZ
• EMDB information: 8117 8118 8119 8120
• Descriptor: Transient receptor potential cation channel subfamily V member 1, capsazepine (2 entities in total)
• Functional Keywords: trp, ion channel, nanodisc, vanilloid, lipid, interaction, transport protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 4
• Total formula weight: 293344.79

Authors

Gao, Y.,Cao, E.,Julius, D.,Cheng, Y. (deposition date: 2016-03-15, release date: 2016-05-25, Last modification date: 2024-03-06)

Primary citation

Gao, Y.,Cao, E.,Julius, D.,Cheng, Y.
TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action.
Nature, 534:347-351, 2016

PubMed Abstract: 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.

PubMed: 27281200
DOI: 10.1038/nature17964

Experimental method

ELECTRON MICROSCOPY (3.43 Å)