Platelet-type von Willebrand disease: Local disorder of the platelet GPIbα β-switch drives high-affinity binding to von Willebrand factor.

ABSTRACT:

Background

Mutations in the β-switch of GPIbα cause gain-of-function in the platelet-type von Willebrand disease. Structures of free and A1-bound GPIbα suggest that the β-switch undergoes a conformational change from a coil to a β-hairpin.

Objectives

Platelet-type von Willebrand disease (VWD) mutations have been proposed to stabilize the β-switch by shifting the equilibrium in favor of the β-hairpin, a hypothesis predicated on the assumption that the complex crystal structure between A1 and GPIbα is the high-affinity state.

Methods

Hydrogen-deuterium exchange mass spectrometry is employed to test this hypothesis using G233V, M239V, G233V/M239V, W230L, and D235Y disease variants of GPIbα. If true, the expectation is a decrease in hydrogen-deuterium exchange within the

SUBMITTER: Tischer A 

PROVIDER: S-EPMC11683816 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature