Von Willebrand Factor is a blood multimeric glycoprotein which is synthetized by endothelials cells of the blood vessels and megakaryocytes of the bone marrow. It is found as big multimer in platelet and endothelials cells. It is the biggest protein in the blood.
When a blood vessel is damaged , some mechanisms come into play in order to stop the bleeding. It is called hemostasis process and the Von Willebrand factor is involved into it.
Synthesis
The protein is encoded by a gene of 52 exons localized on the chromosome 12.
vWF precursor is synthetized as a very large protein in endothelium cells and megakaryocytes.
It undergoes post-translationnal events :
- delete the signal peptide and a large propeptide
- formation of intra and inter chains disulfide bonds
- glycosylations
Dimers are formed in the endoplasmic reticulum (ER) thanks to disulfide bonds formation of C-terminal. These dimers create some multimers via formation N-terminal disulfide bridges between them in the Golgi apparatus.
The mature vWF is synthetized in endothelium cells. It can be immediately secreted (constitutive way) or stocked in the Weibel-Palade body (regulated way).
In the plasma it is cleaved by the processing metalloprotease ADAMTS-13 into smaller multimers. This mechanism cut the peptidyl bond between Y1,605 and M1,606 within the A2 domain of VWF. So, vWF exists as a mixture of disulfide bonded multimers with a size between 500 kDa and 10 000 kDa. This creates a size distribution.
Each multimer is composed of numerous dimers made of two identical subunits which contains several domains : D’-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2
Function
Von Willebrand factor has two mainly functions in diferent phenomenon :
- Coagulation : act as a carrier for the plasma procoagulant co-enzyme, factor VIII. Factor VIII bound to VWF is protected from
inactivation by proteases. Factor VIII is released from VWF by the action of thrombin. The factor VIII is bound to two domains : D'/D3.
- Platelet plug formation : promote platelet adhesion to thrombogenic surfaces and their aggregation. Receptor Gp-1b-IX-V
This factor is also bound to :
- Collagen when the blood vessel is damaged by its A1 and A3 domains. A3 can fixe to collagen I or III
- Platelet integrins αIIb/β3 by the C1 domain (which contains the RGD pattern)
Disease
Idea : touffe (clump) de plaquette
Relevance
Structural highlights
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