Platelet glycoprotein Ib alpha chain, also known as glycoprotein Ib (platelet), alpha polypeptide or CD42b (Cluster of Differentiation 42b), is a protein that in humans is encoded by the GP1BAgene.
Function
Glycoprotein Ib (GP Ib) is a platelet surface membrane glycoprotein receptor composed of a heterodimer, an alpha chain and a beta chain, that are linked by disulfide bonds.[5] The Gp Ib functions as a receptor for von Willebrand factor (VWF). The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX and platelet glycoprotein V to form the glycoprotein Ib-IX-V complex. Binding of the GP Ib-IX-V complex to VWF facilitates initial platelet adhesion to vascular subendothelium after vascular injury,[6] and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis.[7] This gene encodes the alpha subunit. Several polymorphisms and mutations have been described in this gene, some of which are the cause of Bernard–Soulier syndromes and platelet-type von Willebrand disease.[8]
CCP-224, a short PEG-conjugated form of the cyclic peptide OS-1, binds to human GPIb alpha with high affinity and can prevents neutrophil-platelet aggregation in Sickle Cell Disease.[13] In vivo, platelet-mediated thrombus formation can be greatly reduced in arterioles of mice, injured by laser, following an infusion of the OS-1 peptide.[14] The OS-1 peptide prevents binding of GPIb alpha to the VWF A1 domain.[15] The co-crystal structure of GPIb alpha and OS-1 has been reported.[16]
^Benard SA, Smith TM, Cunningham K, Jacob J, DeSilva T, Lin L, et al. (April 2008). "Identification of peptide antagonists to glycoprotein Ibalpha that selectively inhibit von Willebrand factor dependent platelet aggregation". Biochemistry. 47 (16): 4674–4682. doi:10.1021/bi702428q. PMID18363340.
^McEwan PA, Andrews RK, Emsley J (November 2009). "Glycoprotein Ibalpha inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism". Blood. 114 (23): 4883–4885. doi:10.1182/blood-2009-05-224170. PMID19726719.
Further reading
Kunishima S, Kamiya T, Saito H (November 2002). "Genetic abnormalities of Bernard-Soulier syndrome". International Journal of Hematology. 76 (4): 319–327. doi:10.1007/BF02982690. PMID12463594. S2CID23635810.
Girma JP, Takahashi Y, Yoshioka A, Diaz J, Meyer D (October 1990). "Ristocetin and botrocetin involve two distinct domains of von Willebrand factor for binding to platelet membrane glycoprotein Ib". Thrombosis and Haemostasis. 64 (2): 326–332. doi:10.1055/s-0038-1647310. PMID1702906. S2CID27425464.
Andrews RK, Booth WJ, Gorman JJ, Castaldi PA, Berndt MC (October 1989). "Purification of botrocetin from Bothrops jararaca venom. Analysis of the botrocetin-mediated interaction between von Willebrand factor and the human platelet membrane glycoprotein Ib-IX complex". Biochemistry. 28 (21): 8317–8326. doi:10.1021/bi00447a009. PMID2557900.
Wenger RH, Wicki AN, Kieffer N, Adolph S, Hameister H, Clemetson KJ (December 1989). "The 5' flanking region and chromosomal localization of the gene encoding human platelet membrane glycoprotein Ib alpha". Gene. 85 (2): 517–524. doi:10.1016/0378-1119(89)90446-0. PMID2628181.
Wenger RH, Kieffer N, Wicki AN, Clemetson KJ (October 1988). "Structure of the human blood platelet membrane glycoprotein Ib alpha gene". Biochemical and Biophysical Research Communications. 156 (1): 389–395. doi:10.1016/S0006-291X(88)80853-2. PMID2845978.
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