Dynamics of a von Willebrand Factor A1 Autoinhibitory Module with O-Linked Glycans and Its Roles in Regulation of GPIbα Binding.

ABSTRACT: The von Willebrand factor (VWF), a multimeric plasma glycoprotein, binds to the platelet glycoprotein (GPIbα) to initiate the process of primary hemostasis as a response to blood flow alteration in the site of vascular injury. The GPIbα binding site located on the A1 domain of VWF is exposed during the activation of the VWF multimer when it changes from a coiled form to a thread-like, extended form. Though experimental studies have demonstrated that the autoinhibitory module (AIM) connected to the N-/C-termini of the A1 domain is a regulator of VWF activity, the molecular mechanism underlying the regulation of A1-GPIbα binding remains unclear. We modeled the structures of the A1 domain having full-length N-terminal AIM (NAIM) and C-terminal AIM (CAIM) with different types of O-linked glyca

SUBMITTER: Cao Y 

PROVIDER: S-EPMC12010329 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature