52:
496:
Ding, Li; Chen, Jing; Hao, Jinbo; Zhang, Jiahui; Huang, Xuejun; Hu, Fangfang; Wu, Zheng; Liu, Yaru; Li, Wenxin; Cao, Zhijian; Wu, Yingliang; Li, Jian; Li, Shan; Liu, Hongyan; Wu, Wenlong; Chen, Zongyun (May 2017). "Discovery of three toxin peptides with Kv1.3 channel and IL-2 cytokine-inhibiting
338:
Xie, Shujun; Feng, Jing; Yu, Congya; Li, Zhi; Wu, Yingliang; Cao, Zhijian; Li, Wenxin; He, Xiaohua; Xiang, Ming; Han, Song (July 2012). "Identification of a new specific Kv1.3 channel blocker, Ctri9577, from the scorpion
Chaerilus tricostatus".
240:
channels through binding with the S3b-S4 linker within the voltage-sensing domain of the channel, in which four residues are of importance: L275, V276, N280, and V288. Ctri9577’s inhibition of Kv4.3 channel currents is much less potent
393:
Xie, Chang; Li, Tian; Xu, Lingna; Yu, Congya; Cao, Zhijian; Li, Wenxin; Wu, Yingliang (February 2014). "Kv1.3 potassium channel-blocking toxin Ctri9577, novel gating modifier of Kv4.3 potassium channel from the scorpion toxin family".
58:
Ctri9577 contains two alpha-helices (pink), connected to three anti-parallel beta-sheets (yellow), and loops (green). The left helix will be removed in the mature protein. Image adapted from AlphaFold.
194:
of Ctri9577 is based on the typical fold of other scorpion KTxs; it consists of an α-helix connected to three antiparallel β-sheets, which is stabilized with three disulfide bridges (see figure 1).
179:(KTx) commonly form a CSα/β (cysteine-stabilized α-helix-β-sheet) fold. In this motif, an α-helix is connected to two or three antiparallel
661:
264:
channels is voltage-independent. The blocking of the delayed rectifier Kv1.3 is expected to slow down the repolarization phase of the
210:
38:
197:
Ctri9577 has low sequence similarity (<50%) with most other members of the α-KTx15 subfamily., placing it far away on the
666:
191:
275:
233:
656:
542:"Voltage sensor conformations in the open and closed states in rosetta structural models of K + channels"
447:
Mouhat, Stéphanie; Jouirou, Besma; Mosbah, Amor; De Waard, Michel; Sabatier, Jean-Marc (15 March 2004).
553:
167:. The mature peptide of Ctri9577, which is the peptide without the signal sequence, consists of 39
51:
522:
364:
601:"JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes"
632:
581:
514:
478:
411:
356:
198:
176:
172:
164:
622:
612:
571:
561:
506:
468:
460:
403:
348:
265:
557:
627:
600:
576:
541:
473:
448:
497:
activities from Non-Buthidae scorpions, Chaerilus tricostatus and
Chaerilus tryznai".
650:
368:
526:
510:
352:
599:
Zhang, Yiya; Luo, Ji; He, Juan; Rong, Mingqiang; Zeng, Xiongzhi (16 April 2019).
127:
407:
180:
168:
27:
617:
566:
184:
146:
72:
32:
636:
585:
540:
Yarov-Yarovoy, Vladimir; Baker, David; Catterall, William A. (9 May 2006).
518:
482:
429:
415:
360:
285:
shifting steady-state inactivation curves to more positive potentials, and
163:
Ctri9577 is a member of the α-KTx15 subfamily, which specifically target
464:
151:. The name of the toxin derives from the first letter of the genus of
155:(C), species (tri), and the clone number in the cDNA library (9577).
293:
272:
261:
249:
237:
222:
218:
214:
50:
45:
41:
242:
226:
144:
The Ctri9577 toxin is a component of the venom of the scorpion
449:"Diversity of folds in animal toxins acting on ion channels"
171:(4.44 kDa), including six cysteines which form three
396:
175:(see table 1). Other scorpion toxins specific for
546:Proceedings of the National Academy of Sciences
282:shifting activation to more positive potentials
232:of 0.49 ± 0.45 nM. Ctri9577 also modifies the
288:slower recovery from open-state inactivation.
8:
248:-value of 1.34 ± 0.03 μM) than the block of
333:
331:
329:
37:scorpion, which is a potent blocker of the
388:
386:
384:
382:
380:
378:
327:
325:
323:
321:
319:
317:
315:
313:
311:
309:
56:Predicted secondary structure of Ctri9577.
626:
616:
575:
565:
472:
217:channel-blocker and a gating modifier of
61:
305:
430:"AlphaFold Protein Structure Database"
260:The inhibitory effect of Ctri9577 on
7:
213:, which functions both as a potent
14:
209:Ctri9577 is a toxin specific for
211:voltage-gated potassium channels
225:channels are inhibited with an
39:voltage-gated potassium channel
511:10.1016/j.peptides.2017.03.005
353:10.1016/j.peptides.2012.04.023
1:
296:channels will be inhibited.
30:present in the venom of the
109:TRCRTYCIKVHKINSGKCMNSKCVCHP
44:, and a gating modifier of
683:
662:Potassium channel blockers
408:10.1016/j.bbrc.2014.01.094
605:Frontiers in Pharmacology
618:10.3389/fphar.2019.00357
567:10.1073/pnas.0602350103
102:MKLVMRILLTCFLLTTLVIKAEG
59:
271:Ctri9577's effect on
54:
183:and stabilized with
140:Etymology and Source
558:2006PNAS..103.7292Y
453:Biochemical Journal
434:alphafold.ebi.ac.uk
192:secondary structure
64:
667:Ion channel toxins
465:10.1042/BJ20031860
165:potassium channels
62:
60:
552:(19): 7292–7297.
199:phylogenetic tree
185:disulfide bridges
173:disulfide bridges
133:
132:
674:
641:
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589:
579:
569:
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531:
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278:occurs through:
266:action potential
116:Molecular weight
65:
682:
681:
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673:
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671:
657:Scorpion toxins
647:
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92:Signal sequence
17:
12:
11:
5:
680:
678:
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669:
664:
659:
649:
648:
643:
642:
591:
532:
488:
459:(3): 717–726.
439:
421:
402:(3): 406–410.
374:
304:
303:
301:
298:
290:
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286:
283:
257:
256:Mode of action
254:
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228:
221:channels. The
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190:The predicted
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157:
141:
138:
137:
136:
131:
130:
125:
121:
120:
117:
113:
112:
99:
96:Mature protein
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83:
79:
78:
69:
16:Scorpion toxin
15:
13:
10:
9:
6:
4:
3:
2:
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292:As a result,
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34:
29:
25:
21:
608:
604:
594:
549:
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395:
347:(1): 94–99.
344:
340:
291:
270:
259:
208:
196:
189:
162:
152:
145:
143:
108:
107:
105:QIHTNQPCTSNN
104:
101:
95:
91:
71:
55:
31:
23:
19:
18:
169:amino acids
149:tricostatus
77:(scorpion)
75:tricostatus
35:tricostatus
651:Categories
300:References
252:channels.
177:K channels
119:4439.7 Da
90:Sequence (
28:neurotoxin
24:α-KTx15.10
505:: 13–19.
159:Chemistry
153:Chaerilus
147:Chaerilus
82:Subfamily
73:Chaerilus
63:Ctri9577
48:channels.
33:Chaerilus
637:31040778
586:16648251
519:28300672
499:Peptides
483:14674883
416:24472546
369:20286033
361:22580271
341:Peptides
181:β-sheets
85:α-KTx15
20:Ctri9577
628:6476928
611:: 357.
577:1464335
554:Bibcode
527:3475746
474:1224033
124:Uniprot
26:) is a
635:
625:
584:
574:
525:
517:
481:
471:
414:
367:
359:
276:gating
234:gating
205:Target
128:P0DJO5
68:Source
523:S2CID
365:S2CID
294:Kv4.3
273:Kv4.3
262:Kv1.3
250:Kv1.3
238:Kv4.3
223:Kv1.3
219:Kv4.3
215:Kv1.3
46:Kv4.3
42:Kv1.3
633:PMID
582:PMID
515:PMID
479:PMID
412:PMID
357:PMID
623:PMC
613:doi
572:PMC
562:doi
550:103
507:doi
469:PMC
461:doi
457:378
404:doi
400:444
349:doi
236:of
201:.
94:) (
653::
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609:10
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503:91
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477:.
467:.
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451:.
432:.
410:.
398:.
377:^
363:.
355:.
345:36
343:.
308:^
268:.
245:50
243:IC
229:50
227:IC
187:.
639:.
615::
588:.
564::
556::
529:.
509::
485:.
463::
436:.
418:.
406::
371:.
351::
241:(
98:)
22:(
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