Oxidation shuts down an auto-inhibitory mechanism of von Willebrand factor.

ABSTRACT: The blood protein von Willebrand factor (VWF) is a key link between inflammation and pathological thrombus formation. In particular, oxidation of methionine residues in specific domains of VWF due to the release of oxidants in inflammatory conditions has been linked to an increased platelet-binding activity. However, the atomistic details of how methionine oxidation activates VWF have not been elucidated to date. Yet understanding the activation mechanism of VWF under oxidizing conditions can lead to the development of novel therapeutics that target VWF selectively under inflammatory conditions in order to reduce its thrombotic activity while maintaining its haemostatic function. In this manuscript, we used a combination of a dynamic flow assay and molecular dynamics (MD) simulations to in

SUBMITTER: Tsai R 

PROVIDER: S-EPMC8089038 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature