Structural hierarchy of mechanical extensibility in human von Willebrand factor multimers.

ABSTRACT: The von Willebrand factor (VWF) is a multimeric glycoprotein composed of 80- to 120-nm-long protomeric units and plays a fundamental role in mediating platelet function at high shear. The exact nature of the shear-induced structural transitions have remained elusive; uncovering them requires the high-resolution quantitative analysis of gradually extended VWF. Here, we stretched human blood-plasma-derived VWF with molecular combing and analyzed the axial structure of the elongated multimers with atomic force microscopy. Protomers extended through structural intermediates that could be grouped into seven distinct topographical classes. Protomer extension thus progresses through the uncoiling of the C_1-6 domain segment, rearrangements among the N-terminal VWF domains, and unfolding

SUBMITTER: Csanyi MC 

PROVIDER: S-EPMC9798247 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature