Crystal structure of the complex of Glycoprotein Ib alpha and the von Willebrand Factor A1 Domain
Publication Abstract from PubMed
Transient interactions of platelet-receptor glycoprotein Ibalpha (GpIbalpha) and the plasma protein von Willebrand factor (VWF) reduce platelet velocity at sites of vascular damage and play a role in haemostasis and thrombosis. Here we present structures of the GpIbalpha amino-terminal domain and its complex with the VWF domain A1. In the complex, GpIbalpha wraps around one side of A1, providing two contact areas bridged by an area of solvated charge interaction. The structures explain the effects of gain-of-function mutations related to bleeding disorders and provide a model for shear-induced activation. These detailed insights into the initial interactions in platelet adhesion are relevant to the development of antithrombotic drugs.
Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain., Huizinga EG, Tsuji S, Romijn RA, Schiphorst ME, de Groot PG, Sixma JJ, Gros P, Science. 2002 Aug 16;297(5584):1176-9. PMID:12183630
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
- Platelet glycoprotein Ib alpha has a role in the adhesion and migration of leukocytes on vascular thrombus[1].
- Platelet glycoprotein 4 or CD36 functions as a receptor for thrombospondin and collagen [2].
- Platelet glycoprotein 6 ha a role in collagen-induced platelet activation[3].
Disease
Known disease associated with this structure: von Willebrand disease, autosomal dominant OMIM:[193400], von Willebrand disease, autosomal recessive OMIM:[193400], Bernard-Soulier syndrome, benign autosomal dominant OMIM:[606672], Bernard-Soulier syndrome, type A OMIM:[606672], von Willebrand disease, platelet-type OMIM:[606672], Nonarteritic anterior ischemic optic neuropathy, susceptibility to OMIM:[606672]
About this Structure
Initial scene
1m10 is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
- ↑ Simon DI, Chen Z, Xu H, Li CQ, Dong Jf, McIntire LV, Ballantyne CM, Zhang L, Furman MI, Berndt MC, López JA. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med. 2000 Jul 17;192(2):193-204. PMID:10899906 doi:10.1084/jem.192.2.193
- ↑ Kunicki TJ. Platelet membrane glycoproteins and their function: an overview. Blut. 1989 Jul;59(1):30-4. PMID:2665870
- ↑ Moroi M, Jung SM. Platelet glycoprotein VI: its structure and function. Thromb Res. 2004;114(4):221-33. PMID:15381385 doi:10.1016/j.thromres.2004.06.046
