Desialylation of O-glycans activates von Willebrand factor by destabilizing its autoinhibitory module.

ABSTRACT:

Background

The binding of the A1 domain of von Willebrand factor (VWF) to platelet receptor glycoprotein (GP)Ibα defines the VWF activity in hemostasis. Recent studies suggest that sequences flanking A1 form cooperatively an autoinhibitory module (AIM) that reduces the accessibility of the GPIbα binding site on A1. Application of a tensile force induces unfolding of the AIM. Desialylation induces spontaneous binding of plasma VWF to platelets. Most O-glycans in VWF are located around the A1 domain. Removing certain O-glycans in the flanking sequences by site-directed mutagenesis enhances A1 binding to GPIbα and produces an effect similar to type 2B von Willebrand disease in animals.

Objectives

To understand if and how desialylation of O-glycans in the flanking sequences incr

SUBMITTER: Voos KM 

PROVIDER: S-EPMC9134874 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature