Mutual a Domain Interactions in the Force Sensing Protein von Willebrand Factor (VWF)
Sprache des Titels:
VWF is a glycoprotein that plays a central role in hemostasis. It is, amongst others, responsible for platelet adhesion at sites of injury via its A1 domain. The adjacent VWF domain A2 is unfolded under shear upon which it exposes a site cleaved by the protease ADAMTS13 to prevent thrombosis. It has been shown that the A1/platelet interaction is blocked by mutual A1/A2 binding under low shear. Nevertheless, the exact shielding mechanism is not yet clarified. We therefore probed the interaction strength between the A1 and A2 domains and the unfolding behavior of A2 as an indicator of the shielding capacity utilizing single molecule force spectroscopy (SMFS).