2n9z

Solution structure of K1 lobe of double-knot toxin

spinqualitylabelsall models 2n9z Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2n9z is a 1 chain structure with sequence from Cyriopagopus schmidti. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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). Publication Abstract from PubMed Venom toxins are invaluable tools for exploring the structure and mechanisms of ion channels. Here, we solve the structure of double-knot toxin (DkTx), a tarantula toxin that activates the heat-activated TRPV1 channel. We also provide improved structures of TRPV1 with and without the toxin bound, and investigate the interactions of DkTx with the channel and membranes. We find that DkTx 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. We also show that DkTx partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning and channel activation. Finally, we find that the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation. Collectively, our findings reveal a novel mode of toxin-channel recognition that has important implications for the mechanism of thermosensation. Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin.,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 Elife. 2016 Feb 10;5. pii: e11273. doi: 10.7554/eLife.11273. PMID:26880553 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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