vWF

Case study 1: Jirawat Khanongnoi, 2018

Snake venom-metalloproteinases (SVMPs) are the primary factors that disturb hemostasis and cause hemorrhage in the venomous snake bitten subjects. Kaouthiagin is a unique SVMP that binds and cleaves von Willebrand factor (vWF) at a specific peptide bond leading to inhibition of platelet aggregation, which enhances the hemorrhage. Kaouthiagin is a low abundant venom component of Thai cobra (Naja kaouthia); thus, most horse-derived antivenins used for cobra bite treatment do not contain adequate anti-kaouthiagin. This study aimed to produce human single-chain antibody variable fragments (HuscFvs) that bind to and interfere with kaouthiagin activity for further clinical use.

Kaouthiagin was purified from N. kaouthia-holovenom by a single-step gel-filtration chromatography. The selected phages were used to infect Escherichia coli bacteria. Soluble HuscFvs expressed by three phage-transformed-E. coli clones interfered with cobra kaouthiagin binding to human vWF. omputerized simulation indicated that HuscFv of two phage-transformed E. coli clones formed contact interface with kaouthiagin residues at or near catalytic site and effectively inhibited fibrinogenolytic activity of the kaouthiagin.

Fig1. Western blotting patterns of the SDS-PAGE-separated fractions 44–56 probed with 1 μg/mL of recombinant human von Willebrand factor (vWF).

Fig2. Results of HuscFv-mediated inhibition of von Willebrand factor (vWF) binding to kaouthiagin by Western blot analysis.

Case study 2: Yingxue Qi, 2018

Platelet glycoprotein Ibα (GPIbα) extracellular domain, which is part of the receptor complex GPIb-IX-V, plays an important role in tumor metastasis. However, the mechanism through which GPIbα participates in the metastatic process remains unclear. The researchers established a series of screening models and obtained rat anti-mouse GPIbα monoclonal antibodies (mAb) 1D12 and 2B4 that demonstrated potential value in suppressing cancer metastasis. 1D12 and 2B4 affected the von Willebrand factor (vWF)-GPIbα interaction via binding to GPIbα aa 41-50 and aa 277-290 respectively, which markedly inhibited the interaction among platelets, tumor cells, and endothelial cells in vitro, and reduced the mean number of surface nodules in the experimental and spontaneous metastasis models in vivo.

Fig3. The vWF binding was inhibited by 2B4 and 1D12 and detected by flow cytometry. Binding of vWF was detected with FITC-conjugated mouse vWF IgG by flow cytometry and quantitated by mean fluorescence intensity.

Fig4. YQ3 inhibits adhesion and cancer cell-induced platelet activation. The vWF binding was inhibited by YQ3 detected by flow cytometry.

Fig1. Diagram of cellular pathways activated by SARS-CoV-2 S protein and the targets for pharmacological interference. (Alicia Villacampa, 2024)

Fig2. Coronary ruptured site and thrombus interface. (Atsushi Yamashita, 2021)

vWF involved in several pathways and played different roles in them. We selected most pathways vWF participated on our site, such as PIK-Akt signaling pathway, Focal adhesion, ECM-receptor interaction, which may be useful for your reference. Also, other proteins which involved in the same pathway with vWF were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

vWF has several biochemical functions, for example, chaperone binding, collagen binding, glycoprotein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by vWF itself. We selected most functions vWF had, and list some proteins which have the same functions with vWF. You can find most of the proteins on our site.

vWF has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with vWF here. Most of them are supplied by our site. Hope this information will be useful for your research of vWF.

GP1BA; ADAMTS13