Assembling custom side chains on proteoglycans to interrogate their function in living cells

Wenshuang Wang, Naihan Han, Yingying Xu, Yunxue Zhao, Liran Shi, Jorge Filmus and Fuchuan Li ()
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Wenshuang Wang: Shandong University
Naihan Han: Shandong University
Yingying Xu: Shandong University
Yunxue Zhao: Shandong University
Liran Shi: Shandong University
Jorge Filmus: University of Toronto
Fuchuan Li: Shandong University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Proteoglycans (PGs) are composed of a core protein and one or more chains of glycosaminoglycans (GAGs). The highly heterogeneous GAG chains play an irreplaceable role in the functions of PGs. However, the lack of an approach to control the exact structure of GAG chains conjugated to PGs tremendously hinders functional studies of PGs. Herein, by using glypican-3 as a model, we establish an aldehyde tag-based approach to assemble PGs with specific GAG chains on the surface of living cells. We show that the engineered glypican-3 can regulate Wnt and Hedgehog signaling like the wild type. Furthermore, we also present a method for studying the interaction of PGs with their target glycoproteins by combining the assembly of PGs carrying specific GAG chains with metabolic glycan labeling, and most importantly, we obtain evidence of GPC3 directly interacting with Frizzled. In conclusion, this study provides a very useful platform for structural and functional studies of PGs with specific GAG chains.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19765-y

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DOI: 10.1038/s41467-020-19765-y

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