26:
173:. DkTx is a cysteine-rich peptide; such peptides are difficult to synthesise because of their low folding efficiency. This is why structural and functional information about these peptides is limited. DkTx is a 75-amino-acid-peptide consisting of two independently folded head-to-tail ICK domains, which are linked together via a seven amino acid long linker
177:. This compact and rigid structure provides the toxin with a high affinity to bind to its target channel. The linker provides the separation of the two knots and allows them to dock to the channel binding sites concomitantly. The two ICK-motifs are referred to as K1 and K2, and each of them consists of six
268:
produces a large amount of toxins which, although often characterized by the presence of ICK motifs, widely differ in their mode of action. Molecularly, the toxin specifically targets the TRPV1 receptor on the outer edge of the outer pore region of the channel. After binding, DkTx will interact with
281:
Upon binding, the toxin is suggested to induce a prolonged sensation of severe pain, accompanied with neurogenic inflammation due to enduring TRPV1 activation. However, specific behavioural effects remain unknown. In line with the isolated toxin effect, the toxic effects of the crude venom are
255:
Vanillotoxins (VaTx, or
Vanilloids) are toxins that are TRPV1 agonists that target the channel on its outer pore region. For this reason, DkTx is considered a vanillotoxin. Different from the reversible interaction of the other three VaTx toxins (VaTx1, VaTx2 and VaTx3), binding of DkTx is
252:) of DkTx is 0.23 μM. Owing to its bivalent structure, this potency is much higher compared to single K1 and K2 motifs or other vanillotoxins binding to the TRPV1 channel.
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residues into the membrane by forming a complex consisting of the membrane and the toxin, which consequently will lock the TRPV1 channel in the open state.
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181:
residues. For this reason, DkTx is part of the ICK peptide family; however its DNA sequence diverges from other ICK peptides, such as the
535:
Liang S (April 2004). "An overview of peptide toxins from the venom of the
Chinese bird spider Selenocosmia huwena Wang ".
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685:
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Bae C, Anselmi C, Kalia J, Jara-Oseguera A, Schwieters CD, Krepkiy D, et al. (February 2016). Aldrich R (ed.).
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575:"Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin"
25:
157:
The name of DkTx is based on its molecular structure, consisting of two ICK segments, connected via a linker.
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319:"A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain"
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237:, extracellular proteins, and other inflammatory agents. However, binding locations can differ,
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368:"High yield production and refolding of the double-knot toxin, an activator of TRPV1 channels"
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121:, also known as Tau-theraphotoxin-Hs1a or Tau-TRTX-Hs1a, is a toxin found in the venom of the
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241:., capsaicin does not bind to the outer pore region but to the S3-S4 region of the channel.
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209:, which gives it high affinity to its target. The TRPV1 channel is a member of the group of
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ion channels, which are all known to be responsible for sensory signaling, such as
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145:(ICK), is thought to induce excruciating and long-lasting pain by activating the
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Geron M, Kumar R, Zhou W, Faraldo-Gómez JD, Vásquez V, Priel A (December 2018).
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106:
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Proceedings of the
National Academy of Sciences of the United States of America
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The potency of this toxin binding to the TRPV1 channel, as quantified with the
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province of China. This toxin, characterized by its bivalent structure of two
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Bae C, Kalia J, Song I, Yu J, Kim HH, Swartz KJ, Kim JI (2012-12-11).
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Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D (May 2010).
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reported to be mainly nociceptive and inflammatory, but not lethal.
626:"Animal Toxins Providing Insights into TRPV1 Activation Mechanism"
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245:
233:. It can be activated in several ways, such as by noxious heat,
478:"TRPV1 pore turret dictates distinct DkTx and capsaicin gating"
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DkTx can be purified from the venom of the
Chinese bird spider
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irreversible and inflicts persistent TRPV1 channel activity.
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427:"Centipede Venom Peptides Acting on Ion Channels"
229:located in the plasma membrane of nociceptive
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624:Geron M, Hazan A, Priel A (October 2017).
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147:transient receptor potential vanilloid 1
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246:half maximal effective concentration
201:DkTx is a specific TRPV1 receptor
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425:Chu Y, Qiu P, Yu R (April 2020).
225:. TRPV1 itself is a nonselective
137:species primarily living in the
1:
549:10.1016/j.toxicon.2004.02.005
171:reversed-phase chromatography
393:10.1371/journal.pone.0051516
269:the membrane and insert its
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335:10.1016/j.cell.2010.03.052
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23:
143:Inhibitor Cysteine Knots
119:Double-knot toxin (DkTx)
503:10.1073/pnas.1809662115
205:and acts as a bivalent
444:10.3390/toxins12040230
643:10.3390/toxins9100326
488:(50): E11837–E11846.
231:dorsal root ganglions
131:Cyriopagopus schmidti
44:Cyriopagopus schmidti
167:Ornithoctonus huwena
127:Ornithoctonus huwena
686:Invertebrate toxins
592:10.7554/eLife.11273
494:2018PNAS..11511837G
384:2012PLoSO...751516B
123:Chinese Bird spider
681:Ion channel toxins
149:(TRPV1) channel.
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19:Double-knot toxin
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378:(12): e51516.
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329:(5): 834–845.
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691:Neurotoxins
636:(10): 326.
437:(4): E230.
271:hydrophobic
223:nociception
187:huwentoxins
97:Swiss-model
33:Identifiers
675:Categories
585:: e11273.
286:References
93:Structures
88:Search for
266:O. huwena
235:capsaicin
191:hanatoxin
161:Chemistry
153:Etymology
135:tarantula
662:29035314
611:26880553
557:15066414
522:30463948
463:32260499
412:23240036
372:PLOS ONE
353:20510930
277:Toxicity
179:cysteine
107:InterPro
38:Organism
653:5666373
602:4764579
537:Toxicon
513:6294906
490:Bibcode
454:7232367
403:3519854
380:Bibcode
344:2905675
203:agonist
175:peptide
139:Guangxi
103:Domains
73:UniProt
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630:Toxins
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431:Toxins
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221:, and
207:ligand
197:Target
169:using
78:P0CH43
52:Symbol
579:eLife
133:), a
658:PMID
607:PMID
553:PMID
518:PMID
459:PMID
408:PMID
349:PMID
323:Cell
66:5IRX
55:DkTx
648:PMC
638:doi
597:PMC
587:doi
545:doi
508:PMC
498:doi
486:115
449:PMC
439:doi
398:PMC
388:doi
339:PMC
331:doi
327:141
248:(EC
239:e.g
211:TRP
189:or
129:or
61:PDB
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