GP1BA

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. 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, and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis. 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.

Interactions

GP1BA has been shown to interact with YWHAZ and FLNB.

Inhibitors

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. 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. The OS-1 peptide prevents binding of GPIb alpha to the VWF A1 domain. The co-crystal structure of GPIb alpha and OS-1 has been reported.

References

References

1. (August 1987). "Cloning of the alpha chain of human platelet glycoprotein Ib: a transmembrane protein with homology to leucine-rich alpha 2-glycoprotein". Proceedings of the National Academy of Sciences of the United States of America.
2. (June 2002). "Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers". Blood.
3. (July 2003). "Signaling events underlying thrombus formation". Journal of Thrombosis and Haemostasis.
4. "Entrez Gene: GP1BA glycoprotein Ib (platelet), alpha polypeptide".
5. (February 1998). "Human signaling protein 14-3-3zeta interacts with platelet glycoprotein Ib subunits Ibalpha and Ibbeta". Blood.
6. (March 1996). "Identification of a binding sequence for the 14-3-3 protein within the cytoplasmic domain of the adhesion receptor, platelet glycoprotein Ib alpha". The Journal of Biological Chemistry.
7. (January 2000). "Cytoplasmic domains of GpIbalpha and GpIbbeta regulate 14-3-3zeta binding to GpIb/IX/V". Blood.
8. (July 1998). "Human beta-filamin is a new protein that interacts with the cytoplasmic tail of glycoprotein Ibalpha". The Journal of Biological Chemistry.
9. (September 2017). "Glycoprotein Ibα inhibitor (CCP-224) prevents neutrophil-platelet aggregation in Sickle Cell Disease". Blood Advances.
10. (December 2014). "Exploiting the kinetic interplay between GPIbα-VWF binding interfaces to regulate hemostasis and thrombosis". Blood.
11. (April 2008). "Identification of peptide antagonists to glycoprotein Ibalpha that selectively inhibit von Willebrand factor dependent platelet aggregation". Biochemistry.
12. (November 2009). "Glycoprotein Ibalpha inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism". Blood.