5IS0: Structure Of Trpv1 In Complex With Capsazepine, Determined In Lipid Nanodisc

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.
PDB ID: 5IS0Download
MMDB ID: 139591
PDB Deposition Date: 2016/3/15
Updated in MMDB: 2017/09
Experimental Method:
electron microscopy
Resolution: 3.43  Å
Source Organism:
Similar Structures:
Biological Unit for 5IS0: tetrameric; determined by author
Molecular Components in 5IS0
Label Count Molecule
Proteins (4 molecules)
Transient Receptor Potential Cation Channel Subfamily V Member 1(Gene symbol: Trpv1)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB