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Structure, Dynamics, and Interactions of GPI-Anchored Human Glypican-1 with Heparan Sulfates in a Membrane.

Authors
  • Dong, Chuqiao1
  • Choi, Yeol Kyo2
  • Lee, Jumin2
  • Zhang, X Frank1, 3
  • Honerkamp-Smith, Aurelia4
  • Widmalm, Göran5
  • Lowe-Krentz, Linda J2
  • Im, Wonpil2, 3, 6
  • 1 Department of Mechanical Engineering and Mechanicss, Lehigh University, Bethlehem, PA, 18015, United States. , (United States)
  • 2 Department of Biological Sciences, Lehigh University, Bethlehem, PA, 18015, United States. , (United States)
  • 3 Department of Bioengineering, Lehigh University, Bethlehem, PA, 18015, United States. , (United States)
  • 4 Department of Physics, Lehigh University, Bethlehem, PA, 18015, United States. , (United States)
  • 5 Department of Organic Chemistry, Stockholm University, S-106 91 Stockholm, Sweden. , (Sweden)
  • 6 Department of Chemistry, Lehigh University, Bethlehem, PA, 18015, United States. , (United States)
Type
Published Article
Journal
Glycobiology
Publisher
Oxford University Press
Publication Date
Jun 03, 2021
Volume
31
Issue
5
Pages
593–602
Identifiers
DOI: 10.1093/glycob/cwaa092
PMID: 33021626
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Glypican-1 and its heparan sulfate (HS) chains play important roles in modulating many biological processes including growth factor signaling. Glypican-1 is bound to a membrane surface via a glycosylphosphatidylinositol (GPI)-anchor. In this study, we used all-atom molecular modeling and simulation to explore the structure, dynamics, and interactions of GPI-anchored glypican-1, three HS chains, membranes, and ions. The folded glypican-1 core structure is stable, but has substantial degrees of freedom in terms of movement and orientation with respect to the membrane due to the long unstructured C-terminal region linking the core to the GPI-anchor. With unique structural features depending on the extent of sulfation, high flexibility of HS chains can promote multi-site interactions with surrounding molecules near and above the membrane. This study is a first step toward all-atom molecular modeling and simulation of the glycocalyx, as well as its modulation of interactions between growth factors and their receptors. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

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