65:. Knottins are one of three folds in the cystine knot motif; the other closely related knots are the growth factor cystine knot (GFCK) and the cyclic cystine knot (CCK; cyclotide). Types include a) cyclic mobius, b) cyclic bracelet, c) acyclic inhibitor knottins. Cystine knot motifs are found frequently in nature in a plethora of plants, animals, and fungi and serve diverse functions from appetite suppression to anti-fungal activity.
17:
26:
20:
Top: general schematic of the structure of a knottin. A macrocyclic knot is formed by the core of beta strands (arrows) and disulfide bonds (yellow connections between numbered cysteines). Knottins are differentiated from GFCKs by the connectivity of their cysteines. Bottom: The general structure is
95:
Knottins have high stability to pH, heat, and enzymes. Because of their stability and their favorable pharmacodynamic properties, knottins are becoming increasingly popular as protein engineering scaffolds. Moreover, engineered knottins have shown significant promise as therapeutics, imaging agents,
92:. CK peptide components of venoms target voltage-gated ion channels but members of the family also act as antibacterial and haemolytic agents. Plant ICK proteins are often protease inhibitors.
68:
Along with the sections of polypeptide between them, two disulfides form a loop through which the third disulfide bond (linking the 3rd and 6th cysteine in the sequence) passes, forming a
252:
He, W. J.; Chan, L. Y.; Clark, R. J.; Tang, J.; Zeng, G. Z.; Franco, O. L.; Cantacessi, C.; Craik, D. J.; Daly, N. L.; Tan, N. H. (2013). Driscoll, Paul C (ed.).
107:
are the only known mammalian examples of this motif. Both are neuropeptides involved in cell signalling. The former is responsible for hair (fur) colouration.
118:(GFCK) is similar to the ICK but its topology is such that it is the bond between the first and fourth disulfide which threads through the loop.
80:. The motif is also found in some inhibitor proteins found in plants, but the plant and animal motifs are thought to be a product of
610:
600:
85:
590:
493:
Craik, D. J.; Daly, N. L.; Waine, C. (2001). "The cystine knot motif in toxins and implications for drug design".
132:
114:, but lacks the cyclisation of the polypeptide backbone which is present in the latter family. The growth factor
100:
570:
311:
605:
127:
104:
595:
265:
81:
177:
31:
440:
391:
69:
532:(2016). "Engineered knottin peptides as diagnostics, therapeutics, and drug delivery vehicles".
549:
510:
475:
432:
383:
375:
293:
147:
21:
easily seen in this crystal structure of EETI II taken from the protein database (PDB: 2IT7).
541:
529:
502:
467:
422:
365:
283:
273:
62:
197:
352:
Zhu, Shunyi; Darbon, Herve; Dyason, Karin; Verdonck, Fons; Tytgat, Jan (September 2003).
269:
288:
253:
142:
506:
584:
444:
395:
227:
187:
162:
115:
278:
340:
222:
217:
207:
202:
167:
152:
89:
16:
545:
471:
232:
212:
182:
84:. The ICK motif is a very stable protein structure which is resistant to heat
379:
172:
137:
111:
37:
553:
514:
479:
436:
387:
297:
427:
410:
370:
353:
77:
73:
575:
157:
58:
319:
458:
Daly, N. L.; Craik, D. J. (2011). "Bioactive cystine knot proteins".
409:
Zhu, S.; Darbon, H.; Dyason, K.; Verdonck, F.; Tytgat, J. (2003).
24:
15:
254:"Novel Inhibitor Cystine Knot Peptides from Momordica charantia"
192:
72:. The motif is common in invertebrate toxins such as those from
25:
411:"Evolutionary origin of inhibitor cystine knot peptides"
354:"Evolutionary origin of inhibitor cystine knot peptides"
110:The motif is similar to the cyclic cystine knot or
29:MCh-1: A plant inhibitor cystine knot peptide from
341:http://www.mdpi.com/1420-3049/17/11/12533/htm
8:
426:
369:
287:
277:
244:
96:and targeting agents for chemotherapy.
7:
122:Proteins which contain the ICK motif
534:Current Opinion in Chemical Biology
460:Current Opinion in Chemical Biology
339:Reinwarth, Molecules 17:12533 2012
61:structural motif containing three
14:
1:
507:10.1016/S0041-0101(00)00160-4
279:10.1371/journal.pone.0075334
627:
546:10.1016/j.cbpa.2016.08.022
472:10.1016/j.cbpa.2011.02.008
193:Theraphosa leblondi toxin
133:Agouti signalling peptide
101:Agouti signalling peptide
99:The mammalian proteins
611:Cysteine-rich proteins
128:Agouti related peptide
105:Agouti related peptide
47:inhibitor cystine knot
42:
22:
571:The cyclotide webpage
428:10.1096/fj.02-1044fje
371:10.1096/fj.02-1044fje
28:
19:
576:The KNOTTIN Database
82:convergent evolution
530:Cochran, Jennifer R
528:Kintzing, James R;
270:2013PLoSO...875334H
178:Heteroscodratoxin-1
32:Momordica charantia
601:Ion channel toxins
43:
23:
591:Protein structure
421:(12): 1765–1767.
415:The FASEB Journal
364:(12): 1765–1767.
63:disulfide bridges
618:
558:
557:
525:
519:
518:
490:
484:
483:
455:
449:
448:
430:
406:
400:
399:
373:
349:
343:
337:
331:
330:
328:
327:
318:. Archived from
308:
302:
301:
291:
281:
249:
40:
626:
625:
621:
620:
619:
617:
616:
615:
581:
580:
567:
562:
561:
527:
526:
522:
492:
491:
487:
457:
456:
452:
408:
407:
403:
351:
350:
346:
338:
334:
325:
323:
310:
309:
305:
251:
250:
246:
241:
124:
49:(also known as
36:
12:
11:
5:
624:
622:
614:
613:
608:
603:
598:
593:
583:
582:
579:
578:
573:
566:
565:External links
563:
560:
559:
520:
485:
466:(3): 362–368.
450:
401:
344:
332:
303:
264:(10): e75334.
243:
242:
240:
237:
236:
235:
230:
225:
220:
215:
210:
205:
200:
195:
190:
185:
180:
175:
170:
165:
160:
155:
150:
145:
143:Covalitoxin-II
140:
135:
130:
123:
120:
13:
10:
9:
6:
4:
3:
2:
623:
612:
609:
607:
606:Protein folds
604:
602:
599:
597:
594:
592:
589:
588:
586:
577:
574:
572:
569:
568:
564:
555:
551:
547:
543:
539:
535:
531:
524:
521:
516:
512:
508:
504:
500:
496:
489:
486:
481:
477:
473:
469:
465:
461:
454:
451:
446:
442:
438:
434:
429:
424:
420:
416:
412:
405:
402:
397:
393:
389:
385:
381:
377:
372:
367:
363:
359:
358:FASEB Journal
355:
348:
345:
342:
336:
333:
322:on 2015-02-05
321:
317:
316:Cyclotide.com
313:
307:
304:
299:
295:
290:
285:
280:
275:
271:
267:
263:
259:
255:
248:
245:
238:
234:
231:
229:
226:
224:
221:
219:
216:
214:
211:
209:
206:
204:
201:
199:
196:
194:
191:
189:
186:
184:
181:
179:
176:
174:
171:
169:
166:
164:
161:
159:
156:
154:
151:
149:
146:
144:
141:
139:
136:
134:
131:
129:
126:
125:
121:
119:
117:
113:
108:
106:
102:
97:
93:
91:
87:
83:
79:
75:
71:
66:
64:
60:
56:
52:
48:
39:
34:
33:
27:
18:
537:
533:
523:
501:(1): 43–60.
498:
494:
488:
463:
459:
453:
418:
414:
404:
361:
357:
347:
335:
324:. Retrieved
320:the original
315:
306:
261:
257:
247:
228:Vanillotoxin
188:Maurocalcine
163:Guangxitoxin
116:cystine knot
109:
98:
94:
86:denaturation
67:
54:
50:
46:
44:
35:. PDB entry
30:
596:Neurotoxins
540:: 143–150.
223:Tachystatin
218:Stromatoxin
208:Psalmotoxin
203:Phrixotoxin
198:δ-Palutoxin
168:Hainantoxin
153:Grammotoxin
90:proteolysis
585:Categories
326:2018-03-13
239:References
233:Vejocalcin
213:Robustoxin
183:Huwentoxin
380:1530-6860
173:Hanatoxin
138:Albumin I
112:cyclotide
74:arachnids
554:27642714
515:10936622
480:21362584
437:12958203
388:12958203
298:24116036
258:PLOS ONE
78:molluscs
495:Toxicon
445:1117887
396:1117887
312:"Knots"
289:3792974
266:Bibcode
158:GsMTx-4
59:protein
57:) is a
55:Knottin
552:
513:
478:
443:
435:
394:
386:
378:
296:
286:
441:S2CID
392:S2CID
550:PMID
511:PMID
476:PMID
433:PMID
384:PMID
376:ISSN
294:PMID
148:DkTx
103:and
88:and
76:and
70:knot
38:2m2q
542:doi
503:doi
468:doi
423:doi
366:doi
284:PMC
274:doi
53:or
51:ICK
45:An
587::
548:.
538:34
536:.
509:.
499:39
497:.
474:.
464:15
462:.
439:.
431:.
419:17
417:.
413:.
390:.
382:.
374:.
362:17
360:.
356:.
314:.
292:.
282:.
272:.
260:.
256:.
556:.
544::
517:.
505::
482:.
470::
447:.
425::
398:.
368::
329:.
300:.
276::
268::
262:8
41:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
