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

Chuqiao Dong, Yeol Kyo Choi, Jumin Lee, X Frank Zhang, Aurelia Honerkamp-Smith, Göran Widmalm, Linda J Lowe-Krentz, Wonpil Im

Glycobiology 2021 Jun 03

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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: journals.permissions@oup.com.

Citation

Chuqiao Dong, Yeol Kyo Choi, Jumin Lee, X Frank Zhang, Aurelia Honerkamp-Smith, Göran Widmalm, Linda J Lowe-Krentz, Wonpil Im. Structure, Dynamics, and Interactions of GPI-Anchored Human Glypican-1 with Heparan Sulfates in a Membrane. Glycobiology. 2021 Jun 03;31(5):593-602