Factor VIII binding affects the mechanical unraveling of the A2 domain of von Willebrand factor.

ABSTRACT:

Background

Proteolytic cleavage of von Willebrand factor (VWF) by ADAMTS13 is crucial for normal hemostasis. Our previous studies demonstrate that binding of coagulation factor VIII (or FVIII) to VWF enhances the proteolytic cleavage of VWF by ADAMTS13 under shear.

Objectives

Present study aims to determine the mechanism underlying FVIII-mediated enhancing effect on VWF proteolysis by ADAMTS13 under force.

Methods

Single molecular force spectroscopy, atomic force microscopy, and surface plasmon resonance are all used.

Results

Using single molecule force spectroscopy, we show that an addition of FVIII (~5 nmol/L) to D'D3 or D'D3A1 does not significantly alter force-induced unfolding of these fragments; however, an addition of FVIII at the same concentration to D

SUBMITTER: Cao W 

PROVIDER: S-EPMC7789802 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature