Structural highlights
Function
DKTX_CYRSC Selectively activates the heat-activated TRPV1 channel. It binds to TRPV1 in an open state-dependent manner, trapping it there to produce irreversible currents (PubMed:20510930, PubMed:26880553, PubMed:27281200). It binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer (PubMed:26880553, PubMed:27281200). It also partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning (K1) and channel activation (K2) (PubMed:26880553). In addition, the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation (PubMed:26880553).[1] [2] [3]
References
- ↑ Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D. A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain. Cell. 2010 May 28;141(5):834-45. PMID:20510930 doi:10.1016/j.cell.2010.03.052
- ↑ Bae C, Anselmi C, Kalia J, Jara-Oseguera A, Schwieters CD, Krepkiy D, Won Lee C, Kim EH, Kim JI, Faraldo-Gomez JD, Swartz KJ. Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin. Elife. 2016 Feb 10;5. pii: e11273. doi: 10.7554/eLife.11273. PMID:26880553 doi:http://dx.doi.org/10.7554/eLife.11273
- ↑ Gao Y, Cao E, Julius D, Cheng Y. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature. 2016 May 18;534(7607):347-51. doi: 10.1038/nature17964. PMID:27281200 doi:http://dx.doi.org/10.1038/nature17964
