240:
380:
274:
165:
317:(CD42c) contains 181 amino acids. In the extracellular domain (ectodomain), both the N-capping and C-capping regions, which flank the leucine rich repeat sequence, contain two interlocking disulfide bonds. Furthermore, there is only a single leucine-rich repeat giving rise to a much less curved parallel β-coil region as compared to that in GPIbα. GPIbβ contains only one N-glycosylation site (Asn41) and is disulfide linked to GPIbα immediately proximal to the plasma membrane of the platelet via Cys122 located at the junction of the extracellular and transmembrane domains.
321:
367:(CD42a) contains 160 amino acids. The extracellular domain, which also only has a single leucine rich repeat sequence shares more than 45% sequence identity with GPIbβ counterpart. However, the transmembrane and cytoplasmic sequences are considerably different. The GPIX cytoplasmic tail is short consisting of 8 residues and is not known to associate with
289:(Cys) residues Cys4 and Cys17 in the N-capping region, and two disulfide bonds (Cys209-Cys248 and Cys211-Cys264) in the C-capping region. Furthermore, there are seven tandem leucine rich repeats and their flanking sequences in the central parallel β-coil region. This parallel β-coil region is made up of three sided coils stacked in layers and contains two
395:(CD42d) subunit is only weakly associated with the GPIb-IX part of the receptor complex through interactions between the transmembrane domains and has little impact on the surface expression of GPIb-IX, although GPIb-IX is required for efficient expression of GPV. Furthermore, GPV doesn’t appear to be critical for VWF binding or
426:
Bernard
Soulier Syndrome is characterized by little or no expression of GPIb-IX on the surface of platelets which in turn has the same effect on GPV. There have been a number of mutations associated with BSS patients that have been mapped to GPIbα, GPIbβ and GPIX demonstrating that all three subunits
375:
residue (Cys154) located at the junction of the transmembrane and cytoplasmic domains. The extracellular domain of GPV contains 13 leucine rich repeats flanked by N- and C- capping regions both containing two interlocking disulfide bonds. This is followed by a stalk region, the transmembrane sequence
297:
sites. Following the leucine rich repeat domain is the acidic residue-rich sequence containing sulfated tyrosines, the highly O-glycosylated macroglycopeptide, a stalk region of about 40 to 50 residues, a single transmembrane sequence and finally a cytoplasmic tail containing 96 amino acid residues
226:
Human GPIbα is the product of a gene on chromosome 17 specifically 17p12, GPIbβ is the product of a gene on chromosome 22 specifically 22q11.2, while GPV and GPIX are products of genes found on chromosome 3 specifically 3q21 and 3q29 respectively. Under normal conditions, all four molecules are
356:
The GPIbβ cytoplasmic domain has a sequence of 34 amino acids. The region adjacent to the membrane is enriched in basic residues and Ser166 found more distally is phosphorylated and appears to have a role in platelet
387:(TM) domains. The image demonstrates the accessibility of the GPIbα transmembrane helix for direct association with the GPV transmembrane helix as well as the inaccessibility of the GPIX transmembrane helix.
903:
Hollenhorst, Marie A.; Tiemeyer, Katherine H.; Mahoney, Keira E.; Aoki, Kazuhiro; Ishihara, Mayumi; Lowery, Sarah C.; Rangel-Angarita, Valentina; Bertozzi, Carolyn R.; Malaker, Stacy A. (April 2023).
157:, while GPIX associates itself tightly through non-covalent interactions with GPIb. The concomitant expression of all three subunits is required to allow the effective expression of GPIb-IX on the
161:
cell surface and analysis of receptor expression in transfected
Chinese hamster ovary (CHO) cells has further supported that the interaction between these subunits also acts to stabilize them.
239:
231:
of the receptor and are closely associated at the platelet membrane. Typically, a lack of a single subunit significantly decreases the surface expression of the entire receptor complex.
320:
262:
ligand-binding sites of the complex for example: the A1 domain of von
Willebrand factor (VWF) has a binding region as marked in the N-terminal domain of GPIbα; while the
176:
Each of the four subunits (GPIbα, GPIbβ, GPIX and GPV) is part of the leucine rich repeat motif superfamily. These leucine rich repeat sequences tend to be about 24
973:"Synthesis of GPIb beta with novel transmembrane and cytoplasmic sequences in a Bernard–Soulier patient resulting in GPIb-defective signaling in CHO cells"
211:
The four genes that code for the components of the receptor in humans have a simple organization in which the coding sequence is contained within a single
273:
761:"Quaternary organization of GPIb-IX complex and insights into Bernard–Soulier syndrome revealed by the structures of GPIbβ and a GPIbβ/GPIX chimera"
285:
Dissection of the crystal structure of the GPIbα N-terminal leucine rich repeat domain discloses the presence of a single disulfide bond between
115:), GPIbβ (MW 26 kDa), GPIX (MW 20 kDa) and GPV (MW 82kDa). The complex is assembled such that GPIbα, GPIbβ and GPIX form a highly integrated
379:
517:"Glycoprotein Ibalpha inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism"
1023:
411:(BSS), a condition first described by Bernard J and Soulier J.P. It is a rare hereditary bleeding disorder most commonly with an
164:
119:
complex in a 1:2:1 stoichiometry; and this associates weakly with GPV resulting in an overall stoichiometric ratio of 1:1.
408:
705:"Transmembrane domains are critical to the interaction between platelet glycoprotein V and glycoprotein Ib-IX complex"
952:
Bernard J, Soulier JP (1948). "Sur une nouvelle variete de dystrophie thrombocythaire hemorragipare congenitale".
407:
Abnormalities of the GPIb-V-IX complex result in abnormal appearance and functioning of platelets resulting in
86:, and the life cycle of platelets, and is implicated in a number of thrombotic pathological processes such as
38:. It primarily functions to mediate the first critical step in platelet adhesion, by facilitating binding to
1018:
266:
binding site is contained in a conformationally flexible acidic residue-rich sequence containing sulfated
653:"Glycoprotein Ibalpha forms disulfide bonds with 2 glycoprotein Ibbeta subunits in the resting platelet"
91:
39:
27:
192:
disulfide loop structures. Nevertheless, even though these structural similarities exist, distinctive
384:
333:
227:
expressed exclusively in the platelet lineage. GPIbα, GPIbβ and GPIX are necessary for the effective
412:
396:
349:
127:
994:
934:
885:
844:
790:
734:
682:
630:
586:
538:
494:
329:
248:
984:
924:
916:
875:
834:
824:
780:
772:
724:
716:
672:
664:
620:
578:
569:
López JA, Andrews RK, Afshar-Kharghan V, Berndt MC (June 1998). "Bernard-Soulier syndrome".
528:
484:
476:
108:
364:
294:
154:
609:"Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane"
929:
904:
839:
812:
785:
760:
729:
704:
677:
652:
489:
464:
345:
325:
303:
278:
244:
181:
169:
31:
153:
interactions. The GPIbα subunit is linked to two GPIbβ subunits via membrane-proximal
1012:
989:
972:
880:
863:
720:
416:
368:
259:
123:
112:
168:
View from the top of the membrane proximal portion of GPIb-IX indicating in red the
358:
228:
205:
150:
43:
625:
608:
258:(CD42b) consisting of 610 amino acids is the major subunit and contains all known
776:
668:
533:
516:
419:, a reduced number of very large platelets (macrothrombocytopenia) and defective
341:
220:
197:
177:
135:
920:
251:
of the GPIbα N-terminal domain including the VWF A1 and thrombin binding sites.
905:"Comprehensive analysis of platelet glycoprotein Ibα ectodomain glycosylation"
651:
Luo SZ, Mo X, Afshar-Kharghan V, Srinivasan S, López JA, Li R (January 2007).
582:
420:
392:
337:
290:
189:
185:
131:
83:
79:
67:
59:
134:(extracellular domain), a single transmembrane helix, and a relatively short
267:
139:
71:
63:
35:
998:
938:
889:
848:
829:
794:
738:
686:
542:
498:
427:
are required for effective surface expression of the complex on platelets.
634:
590:
372:
286:
263:
158:
146:
75:
55:
50:
for the GPIb-V-IX receptor is VWF, it can also bind to a number of other
24:
465:"The organizing principle of the platelet glycoprotein Ib-IX-V complex"
116:
51:
480:
215:. This is with the exception of the gene for GPIbβ, which contains an
299:
216:
201:
87:
47:
813:"Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy)"
378:
344:
sit to the right and the convex loops are positioned to the left.
319:
314:
272:
255:
238:
193:
163:
212:
42:(VWF) on damaged sub-endothelium under conditions of high fluid
145:
The quaternary stabilization of the receptor is facilitated by
107:
GPIb-IX-V consists of four different subunits namely: GPIbα (
607:
Du X, Beutler L, Ruan C, Castaldi PA, Berndt MC (May 1987).
971:
Strassel C, David T, Eckly A, et al. (January 2006).
759:
McEwan PA, Yang W, Carr KH, et al. (November 2011).
864:"Qualitative disorders of platelets and megakaryocytes"
302:
residues such as Ser587, Ser590 and Ser609 that can be
281:
depicting the various components of the GPIbα subunit.
376:
and a short cytoplasmic tail rich in basic residues.
515:McEwan PA, Andrews RK, Emsley J (November 2009).
806:
804:
754:
752:
750:
748:
703:Mo X, Liu L, López JA, Li R (September 2012).
698:
696:
646:
644:
510:
508:
458:
456:
454:
452:
450:
448:
446:
444:
442:
440:
602:
600:
564:
562:
560:
558:
556:
554:
552:
415:inheritance and diagnosed based on prolonged
34:and exclusively functional on the surface of
8:
293:residues (Asn21 and Asn159), which serve as
988:
928:
879:
838:
828:
784:
728:
676:
624:
532:
488:
180:in length either occurring singly or in
122:Each subunit of the complex is a type I
436:
340:is positioned at the top, the concave
78:. GPIb-IX-V offers a critical role in
909:Journal of Thrombosis and Haemostasis
7:
383:Interaction of GPV with GPIb-IX via
208:that make up the GPIb-V-IX complex.
14:
423:-induced platelet agglutination.
126:(TM) protein which consists of a
990:10.1111/j.1538-7836.2005.01654.x
881:10.1111/j.1538-7836.2005.01428.x
721:10.1111/j.1538-7836.2012.04841.x
1:
626:10.1182/blood.V69.5.1524.1524
463:Li R, Emsley J (April 2013).
777:10.1182/blood-2011-05-356253
669:10.1182/blood-2006-05-024091
534:10.1182/blood-2009-05-224170
371:proteins. There is also a
54:in the circulation such as
1040:
921:10.1016/j.jtha.2023.01.009
862:Nurden AT (August 2005).
583:10.1182/blood.V91.12.4397
409:Bernard–Soulier syndrome
352:are indicated in yellow.
196:that exist on different
172:between GPIbα and GPIbβ.
70:, high molecular weight
1024:Transmembrane receptors
219:10 bases following the
46:. Although the primary
30:complex originating in
830:10.1186/1750-1172-1-46
388:
353:
282:
252:
173:
382:
323:
276:
242:
184:flanked by conserved
167:
109:molecular weight (MW)
92:myocardial infarction
40:von Willebrand factor
334:extracellular domain
817:Orphanet J Rare Dis
413:autosomal recessive
397:signal transduction
128:leucine-rich repeat
98:Molecular structure
977:J. Thromb. Haemost
868:J. Thromb. Haemost
709:J. Thromb. Haemost
469:J. Thromb. Haemost
417:skin-bleeding time
389:
354:
283:
253:
174:
481:10.1111/jth.12144
330:crystal structure
249:crystal structure
21:GPIb-IX-V complex
16:Membrane receptor
1031:
1003:
1002:
992:
968:
962:
961:
949:
943:
942:
932:
900:
894:
893:
883:
859:
853:
852:
842:
832:
811:Lanza F (2006).
808:
799:
798:
788:
771:(19): 5292–301.
756:
743:
742:
732:
700:
691:
690:
680:
648:
639:
638:
628:
604:
595:
594:
577:(12): 4397–418.
566:
547:
546:
536:
512:
503:
502:
492:
460:
310:GPIbβ, GPIX, GPV
138:tail that lacks
1039:
1038:
1034:
1033:
1032:
1030:
1029:
1028:
1009:
1008:
1007:
1006:
970:
969:
965:
951:
950:
946:
915:(4): 995–1009.
902:
901:
897:
861:
860:
856:
810:
809:
802:
758:
757:
746:
702:
701:
694:
650:
649:
642:
606:
605:
598:
568:
567:
550:
514:
513:
506:
462:
461:
438:
433:
405:
403:Role in disease
361:rearrangement.
346:Disulfide bonds
312:
298:which includes
295:N-glycosylation
237:
170:disulfide bonds
155:disulfide bonds
105:
100:
17:
12:
11:
5:
1037:
1035:
1027:
1026:
1021:
1011:
1010:
1005:
1004:
963:
944:
895:
874:(8): 1773–82.
854:
800:
744:
715:(9): 1875–86.
692:
640:
596:
548:
527:(23): 4883–5.
504:
435:
434:
432:
429:
404:
401:
328:depicting the
326:ribbon diagram
311:
308:
304:phosphorylated
279:ribbon diagram
247:depicting the
245:ribbon diagram
236:
233:
182:tandem repeats
104:
101:
99:
96:
32:megakaryocytes
15:
13:
10:
9:
6:
4:
3:
2:
1036:
1025:
1022:
1020:
1019:Glycoproteins
1017:
1016:
1014:
1000:
996:
991:
986:
983:(1): 217–28.
982:
978:
974:
967:
964:
959:
955:
954:Sem Hop Paris
948:
945:
940:
936:
931:
926:
922:
918:
914:
910:
906:
899:
896:
891:
887:
882:
877:
873:
869:
865:
858:
855:
850:
846:
841:
836:
831:
826:
822:
818:
814:
807:
805:
801:
796:
792:
787:
782:
778:
774:
770:
766:
762:
755:
753:
751:
749:
745:
740:
736:
731:
726:
722:
718:
714:
710:
706:
699:
697:
693:
688:
684:
679:
674:
670:
666:
662:
658:
654:
647:
645:
641:
636:
632:
627:
622:
619:(5): 1524–7.
618:
614:
610:
603:
601:
597:
592:
588:
584:
580:
576:
572:
565:
563:
561:
559:
557:
555:
553:
549:
544:
540:
535:
530:
526:
522:
518:
511:
509:
505:
500:
496:
491:
486:
482:
478:
475:(4): 605–14.
474:
470:
466:
459:
457:
455:
453:
451:
449:
447:
445:
443:
441:
437:
430:
428:
424:
422:
418:
414:
410:
402:
400:
398:
394:
386:
385:transmembrane
381:
377:
374:
370:
369:intracellular
366:
362:
360:
351:
347:
343:
339:
335:
332:of the GPIbβ
331:
327:
322:
318:
316:
309:
307:
305:
301:
296:
292:
288:
280:
275:
271:
269:
265:
261:
260:extracellular
257:
250:
246:
241:
234:
232:
230:
224:
222:
218:
214:
209:
207:
204:code for the
203:
199:
195:
191:
187:
183:
179:
171:
166:
162:
160:
156:
152:
148:
143:
141:
137:
133:
129:
125:
124:transmembrane
120:
118:
114:
110:
102:
97:
95:
93:
89:
85:
81:
77:
73:
69:
65:
61:
57:
53:
49:
45:
41:
37:
33:
29:
26:
23:is a profuse
22:
980:
976:
966:
960:: 3217–3223.
957:
953:
947:
912:
908:
898:
871:
867:
857:
820:
816:
768:
764:
712:
708:
663:(2): 603–9.
660:
656:
616:
612:
574:
570:
524:
520:
472:
468:
425:
406:
390:
363:
359:cytoskeletal
355:
313:
284:
254:
229:biosynthesis
225:
210:
206:polypeptides
175:
151:non-covalent
144:
121:
106:
44:shear stress
20:
18:
350:LRR regions
348:present in
221:start codon
198:chromosomes
178:amino acids
136:cytoplasmic
74:as well as
1013:Categories
431:References
421:ristocetin
338:N-terminus
291:asparagine
190:C-terminal
186:N-terminal
142:activity.
132:ectodomain
84:metastasis
80:thrombosis
68:factor XII
60:P-selectin
342:β-strands
268:tyrosines
140:enzymatic
72:kininogen
64:factor XI
36:platelets
999:16409472
939:36740532
930:10065957
890:16102044
849:17109744
795:21908432
739:22759073
687:17008541
543:19726719
499:23336709
373:cysteine
287:cysteine
264:thrombin
159:platelet
147:covalent
103:Overview
76:bacteria
56:thrombin
28:receptor
25:membrane
840:1660532
786:3217411
730:3499136
678:1785083
635:2436691
591:9616133
490:3696474
200:of the
117:protein
52:ligands
997:
937:
927:
888:
847:
837:
823:: 46.
793:
783:
737:
727:
685:
675:
633:
589:
541:
497:
487:
336:. The
300:serine
217:intron
202:genome
130:(LRR)
88:stroke
48:ligand
765:Blood
657:Blood
613:Blood
571:Blood
521:Blood
315:GPIbβ
256:GPIbα
235:GPIbα
194:genes
995:PMID
935:PMID
886:PMID
845:PMID
791:PMID
735:PMID
683:PMID
631:PMID
587:PMID
539:PMID
495:PMID
391:The
365:GPIX
213:exon
188:and
149:and
111:135
19:The
985:doi
925:PMC
917:doi
876:doi
835:PMC
825:doi
781:PMC
773:doi
769:118
725:PMC
717:doi
673:PMC
665:doi
661:109
621:doi
579:doi
529:doi
525:114
485:PMC
477:doi
393:GPV
113:kDa
90:or
1015::
993:.
979:.
975:.
958:24
956:.
933:.
923:.
913:21
911:.
907:.
884:.
870:.
866:.
843:.
833:.
819:.
815:.
803:^
789:.
779:.
767:.
763:.
747:^
733:.
723:.
713:10
711:.
707:.
695:^
681:.
671:.
659:.
655:.
643:^
629:.
617:69
615:.
611:.
599:^
585:.
575:91
573:.
551:^
537:.
523:.
519:.
507:^
493:.
483:.
473:11
471:.
467:.
439:^
399:.
324:A
306:.
277:A
270:.
243:A
223:.
94:.
82:,
66:,
62:,
58:,
1001:.
987::
981:4
941:.
919::
892:.
878::
872:3
851:.
827::
821:1
797:.
775::
741:.
719::
689:.
667::
637:.
623::
593:.
581::
545:.
531::
501:.
479::
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