Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics.

ABSTRACT:

Background

A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1. These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance. The inhibitory mechanism remains unresolved as to whether inhibition is due to steric exclusion by OLGs or a direct self-association interaction that stabilizes the domain.

Objectives

The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-

SUBMITTER: Tischer A 

PROVIDER: S-EPMC6940534 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature