Structural hierarchy of mechanical extensibility in human von Willebrand factor multimers

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 hig...

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Bibliographic Details
Published in:Protein science 2023-01, Vol.32 (1), p.e4535-n/a
Main Authors: Csányi, Mária Csilla, Salamon, Pál, Feller, Tímea, Bozó, Tamás, Hársfalvi, Jolán, Kellermayer, Miklós S. Z.
Format: Article
Language:English
Subjects:
Atomic force microscopy
conformation
Domains
Elongated structure
Full‐length Paper
Full‐length Papers
Glycoproteins
Humans
Intermediates
Molecular structure
Protein Subunits
receding meniscus
Structural hierarchy
topography
Von Willebrand factor
von Willebrand Factor - chemistry
VWF protomer
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Summary: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 C1–6 domain segment, rearrangements among the N‐terminal VWF domains, and unfolding and elastic extension of the A2 domain. The least and most extended protomer conformations were localized at the ends and the middle of the multimer, respectively, revealing an apparent necking phenomenon characteristic of plastic‐material behavior. The structural hierarchy uncovered here is likely to provide a spatial control mechanism to the complex functions of VWF.
ISSN:0961-8368
1469-896X
DOI:10.1002/pro.4535