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

Autor: Csányi MC; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary., Salamon P; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary., Feller T; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary., Bozó T; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary., Hársfalvi J; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary., Kellermayer MSZ; Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
Jazyk: angličtina
Zdroj: Protein science : a publication of the Protein Society [Protein Sci] 2023 Jan; Vol. 32 (1), pp. e4535.
DOI: 10.1002/pro.4535
Abstrakt: 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 and elastic extension of the A 2 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.
(© 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)
Databáze: MEDLINE
Externí odkaz: