pH-dependent conformation of multimeric von Willebrand factor

• Type of Material: Article
• Authors: Ian W Smith, Aflac Cancer and Blood Disorders Center; Ernest T Parker, Aflac Cancer and Blood Disorders Center; Pete Lollar, Aflac Cancer and Blood Disorders Center
• Language: English
• Date: 2023-06-07
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2022009359
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 7
• Issue: 11
• Start Page: 2554
• End Page: 2557
• Keywords: Science & Technology; Hematology; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology

Abstract

von Willebrand factor (VWF) is a multimeric plasma glycoprotein necessary for normal vertebrate hemostasis. It is a linear homopolymer consisting of a variable number of concatenated ∼280 kDa subunits.1 The conformation of VWF multimers has been controversial. The spectrum of macromolecular conformations ranges from a globular particle to a random coil to a rod-like particle2 (p. 261). Based on electron microscopy, atomic force microscopy, small-angle neutron scattering, total internal reflection fluorescence microscopy, and theoretical studies, the conformation of multimeric VWF under static conditions has been variably described as a “ball-of-yarn,”3 a “tangled coil,”4 a “compact, bird’s nest,”1 a “compact fuzz ball,”5 “compact and globular,”6 and a “dense globule.”7 These descriptions suggest that the conformation of VWF is a function of strong attractive forces between subunits.8 However, recently the characterization of VWF at pH 7.4 by sedimentation velocity analytical ultracentrifugation, dynamic light scattering (DLS), and multiangle light scattering (MALS) have challenged this notion.9,10 Conformation plots of the sedimentation coefficient, diffusion coefficient, and radius of gyration as a function of molecular weight were consistent with a random coil conformation and not a folded, globular conformation.