143:) with the amino acid resides in the aromatic box, located on the principal face of the binding site. Another essential interaction occurs between the agonist and a tyrosine on loop C. Upon interaction, the loop undergoes a conformational change and rotates down to cap the molecule in the binding site.
104:
All subunits consist of a large conserved extracellular N-terminal domain, three highly conserved transmembrane domains, a cytoplasmic loop of variable size and amino acid sequence, and a fourth transmembrane region with a relatively short and variable extracellular C-terminal domain.
172:(at 9 Å) shows that the opening is caused by rotation at the M2 domain, but other studies on crystal structures of these receptors has shown that the opening could be a result from a M2 tilt which leads to pore dilation and a quaternary turn of the entire pentameric receptor.
128:(AChBP) determined that the binding sites consist of six loops, with the first three forming the principal face and the next three forming the complementary face. The last loop on the principal face wraps over the ligand in the active receptor. This site is also abundant in
77:
which form a pentameric arrangement around a central pore. There are usually 2 alpha subunits and 3 other beta, gamma, or delta subunits (some consist of 5 alpha subunits). The name of the family refers to a characteristic loop formed by 13 highly conserved
167:
and gating domains. Once the agonist binds it brings about conformational changes (including moving a beta sheet of the amino-terminal domain, and outward movement from loops 2, F and cys-loop which are tied to the M2-M3 linker and pull the channel open).
116:
Each subunit contains four membrane-spanning alpha helices (M1, M2, M3, M4). The pore is formed primarily by the M2 helices. The M3-M4 linker is the intracellular domain that binds the cytoskeleton.
97:, but are part of a larger family of pentameric ligand-gated ion channels. Only the Cys-loop clade includes the pair of bridging cysteine residues. The larger superfamily includes bacterial (e.g.
135:
Recent literature indicates that the Trp residue on loop B is crucial for both agonist and antagonist binding. The neurotransmitter is taken into the binding site where it interacts (through
732:
830:
259:"Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels"
725:
124:
Most knowledge about cys-loop receptors comes from inferences made while studying various members of the family. Research on the structures of
147:
213:"Assessment of the number of free cysteines and isolation and identification of cystine-containing peptides from acetylcholine receptor"
472:"Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations"
423:"Functional probes of drug-receptor interactions implicated by structural studies: cys-loop receptors provide a fertile testing ground"
101:) as well as non-Cys-loop eukaryotic receptors, and is referred to as "pentameric ligand-gated ion channels", or "Pro-loop receptors".
718:
1141:
1129:
1161:
1038:
36:
1495:
570:"Advances and hold-ups in the study of structure, function and regulation of cys-loop ligand-gated ion channels and receptors"
1174:
1490:
159:
Through research done on nicotinic acetylcholine receptors it has been determined that the channels are activated through
1480:
1196:
1153:
66:
140:
1505:
996:
150:
Image of nicotinic acetylcholine receptor - the most commonly studied member of the Cys-Loop receptor superfamily
710:
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30:
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129:
125:
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422:
367:
Sine S; Engel A (2006). "Recent advances in Cys-loop receptor structure and function".
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212:
236:
658:"Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function"
83:
536:
388:
228:
1345:
1340:
1089:
310:"Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors"
438:
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797:
792:
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782:
145:
1028:
98:
714:
521:"Allosteric activation mechanism of the cys-loop receptors"
613:"Principles of agonist recognition in Cys-loop receptors"
1409:
1396:
1356:
1291:
1221:
1209:
1187:
1037:
987:
813:
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756:
519:Huang, Y; Zhang, JL; Wu, W; Chang, YC (June 2009).
416:
414:
257:Tasneem A, Iyer L, Jakobsson E, Aravind L (2004).
421:Van Arnam, EB; Dougherty, DA (August 14, 2014).
109:bind at the interface between subunits in the
726:
8:
470:Bourne, Y; et al. (October 19, 2005).
1406:
1218:
762:
733:
719:
711:
90:near the N-terminal extracellular domain.
681:
638:
628:
593:
544:
495:
446:
343:
333:
284:
274:
211:Kellaris, Kennan Vincent (Apr 18, 1989).
611:Pless, SA; Lynagh, T (April 24, 2014).
203:
73:. These receptors are composed of five
656:Albuquerque, EX; et al. (2009).
93:Cys-loop receptors are known only in
7:
308:Jaiteh M, Taly A, Hénin J (2016).
25:
706:Cys-Loop Ligand Gated Channels
568:Yakel, J (February 15, 2010).
427:Journal of Medicinal Chemistry
126:acetylcholine binding proteins
1:
86:(Cys) residues, which form a
586:10.1113/jphysiol.2009.185488
335:10.1371/journal.pone.0151934
1522:
674:10.1152/physrev.00015.2008
525:Acta Pharmacologica Sinica
1293:Voltage- and ligand-gated
750:ligand-gated ion channels
574:The Journal of Physiology
630:10.3389/fphys.2014.00160
580:(588 (Pt. 4)): 555–556.
488:10.1038/sj.emboj.7600828
31:ligand-gated ion channel
1039:Nicotinic acetylcholine
617:Frontiers in Physiology
192:Receptor (biochemistry)
161:allosteric interactions
37:nicotinic acetylcholine
1496:Molecular neuroscience
276:10.1186/gb-2004-6-1-r4
151:
746:cell surface receptor
149:
1491:Ionotropic receptors
1411:Purinergic receptors
111:extracellular domain
537:10.1038/aps.2009.51
389:10.1038/nature04708
381:2006Natur.440..448S
326:2016PLoSO..1151934J
229:10.1021/bi00434a048
170:Electron microscopy
1179:β1δε - Muscle type
758:Cys-loop receptors
187:Nicotinic agonists
152:
18:Cys-loop receptors
1481:Electrophysiology
1468:
1467:
1464:
1463:
1392:
1391:
1223:Ligand-gated only
1205:
1204:
482:(20): 3635–3646.
439:10.1021/jm500023m
433:(15): 6289–6300.
130:aromatic residues
107:Neurotransmitters
16:(Redirected from
1513:
1506:Protein families
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476:The EMBO Journal
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223:(8): 3469–3482.
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141:cation-π bonding
75:protein subunits
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1170:- Ganglion type
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35:is composed of
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1501:Neurochemistry
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1197:Zinc-activated
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767:5-HT/serotonin
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700:External links
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531:(6): 663–672.
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263:Genome Biology
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155:Channel gating
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88:disulfide bond
67:zinc-activated
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19:
1486:Ion channels
1401:
1365:
1357:
1292:
1222:
1188:
1126:
1046:
665:
661:
620:
616:
577:
573:
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240:. Retrieved
220:
217:Biochemistry
216:
206:
163:between the
158:
134:
123:
115:
103:
92:
82:between two
28:
26:
742:Ion channel
662:Physiol Rev
182:Ion channel
80:amino acids
33:superfamily
1475:Categories
1214:glutamates
1211:Ionotropic
1127:pentamers:
242:3 February
198:References
95:eukaryotes
1047:monomers:
269:(1): R4.
71:receptors
29:Cys-loop
1358:‘Orphan’
692:19126755
649:24795655
604:20173078
555:19444220
506:16193063
457:24568098
397:16554804
354:26986966
314:PLOS ONE
295:15642096
176:See also
137:hydrogen
84:cysteine
1256:Kainate
989:Glycine
683:2713585
640:4006026
623:: 160.
595:2828129
546:4002373
497:1276711
448:4136689
405:3899722
377:Bibcode
345:4795631
322:Bibcode
237:2742850
165:binding
120:Binding
56:glycine
690:
680:
647:
637:
602:
592:
553:
543:
504:
494:
455:
445:
403:
395:
369:Nature
352:
342:
293:
286:549065
283:
235:
69:(ZAC)
65:, and
401:S2CID
1366:GluD
1301:NMDA
1231:AMPA
1189:Zinc
1175:(α1)
1166:(β4)
1162:(α1)
1154:(α7)
1146:(β2)
1142:(α4)
1134:(β4)
1130:(α3)
949:GABA
823:GABA
815:GABA
775:5-HT
688:PMID
645:PMID
600:PMID
551:PMID
502:PMID
453:PMID
393:PMID
350:PMID
291:PMID
244:2021
233:PMID
139:and
99:GLIC
60:5-HT
48:GABA
41:GABA
27:The
1419:P2X
1398:ATP
1346:L1B
1341:L1A
1090:α10
678:PMC
670:doi
635:PMC
625:doi
590:PMC
582:doi
578:588
541:PMC
533:doi
492:PMC
484:doi
443:PMC
435:doi
385:doi
373:440
340:PMC
330:doi
281:PMC
271:doi
225:doi
1477::
1336:3B
1331:3A
1326:2D
1321:2C
1316:2B
1311:2A
1110:β4
1105:β3
1100:β2
1095:β1
1085:α9
1080:α7
1075:α6
1070:α5
1065:α4
1060:α3
1055:α2
1050:α1
953:-ρ
748::
744:,
686:.
676:.
666:89
664:.
660:.
643:.
633:.
619:.
615:.
598:.
588:.
576:.
572:.
549:.
539:.
529:30
527:.
523:.
500:.
490:.
480:24
478:.
474:.
451:.
441:.
431:57
429:.
425:.
413:^
399:.
391:.
383:.
371:.
348:.
338:.
328:.
318:11
316:.
312:.
289:.
279:.
265:.
261:.
231:.
221:28
219:.
215:.
132:.
113:.
58:,
54:,
52:-ρ
46:,
39:,
1454:7
1449:6
1444:5
1439:4
1434:3
1429:2
1424:1
1400:-
1381:2
1379:δ
1373:1
1371:δ
1306:1
1281:5
1276:4
1271:3
1266:2
1261:1
1252:)
1250:4
1245:3
1240:2
1235:1
1233:(
1177:2
1168:3
1164:2
1156:5
1148:3
1144:2
1136:3
1132:2
1120:ε
1115:δ
1029:β
1023:4
1021:α
1015:3
1013:α
1007:2
1005:α
999:1
997:α
976:3
974:ρ
968:2
966:ρ
960:1
958:ρ
951:A
942:θ
937:π
932:ε
927:δ
921:3
919:γ
913:2
911:γ
905:1
903:γ
897:3
895:β
889:2
887:β
881:1
879:β
873:6
871:α
865:5
863:α
857:4
855:α
849:3
847:α
841:2
839:α
833:1
831:α
825:A
803:E
798:D
793:C
788:B
783:A
777:3
734:e
727:t
720:v
694:.
672::
651:.
627::
621:5
606:.
584::
557:.
535::
508:.
486::
459:.
437::
407:.
387::
379::
356:.
332::
324::
297:.
273::
267:6
246:.
227::
62:3
50:A
43:A
20:)
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