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2naj

From Proteopedia

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Current revision

Solution structure of K2 lobe of double-knot toxin

Structural highlights

2naj 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.
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).^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2naj"

@@ Line 1: / Line 1: @@
 ==Solution structure of K2 lobe of double-knot toxin==
-<StructureSection load='2naj' size='340' side='right' caption='[[2naj]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2naj' size='340' side='right'caption='[[2naj]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2naj]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NAJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NAJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2naj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cyriopagopus_schmidti Cyriopagopus schmidti]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NAJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NAJ FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2naj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2naj OCA], [http://pdbe.org/2naj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2naj RCSB], [http://www.ebi.ac.uk/pdbsum/2naj PDBsum]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2naj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2naj OCA], [https://pdbe.org/2naj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2naj RCSB], [https://www.ebi.ac.uk/pdbsum/2naj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2naj ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/DKTX_CYRSC 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).<ref>PMID:20510930</ref> <ref>PMID:26880553</ref> <ref>PMID:27281200</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 21: @@
 __TOC__
 </StructureSection>
-[[Category: Anselmi, C]]
+[[Category: Cyriopagopus schmidti]]
-[[Category: Bae, C]]
+[[Category: Large Structures]]
-[[Category: Faraldo-Gomez, J D]]
+[[Category: Anselmi C]]
-[[Category: Jara-Oseguera, A]]
+[[Category: Bae C]]
-[[Category: Kalia, J]]
+[[Category: Faraldo-Gomez JD]]
-[[Category: Kim, E H]]
+[[Category: Jara-Oseguera A]]
-[[Category: Kim, J I]]
+[[Category: Kalia J]]
-[[Category: Krepkiy, D]]
+[[Category: Kim EH]]
-[[Category: Lee, C W]]
+[[Category: Kim JI]]
-[[Category: Schwieters, C D]]
+[[Category: Krepkiy D]]
-[[Category: Swartz, K J]]
+[[Category: Lee CW]]
-[[Category: Dktx]]
+[[Category: Schwieters CD]]
-[[Category: Double-knot toxin]]
+[[Category: Swartz KJ]]
-[[Category: Ick]]
-[[Category: K2]]
-[[Category: Spider]]
-[[Category: Tarantula]]
-[[Category: Toxin]]
-[[Category: Trpv1]]

2naj

From Proteopedia

Current revision

Solution structure of K2 lobe of double-knot toxin

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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