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- Title
Assembling custom side chains on proteoglycans to interrogate their function in living cells.
- Authors
Wang, Wenshuang; Han, Naihan; Xu, Yingying; Zhao, Yunxue; Shi, Liran; Filmus, Jorge; Li, Fuchuan
- 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. Currently, it is not possible to generate proteoglycans displaying glycosaminoglycan chains with specific structures. Here the authors show that by using an aldehyde tag-based methodology it is possible to insert these specific chains onto proteoglycans expressed on the cell surface.
- Subjects
PROTEOGLYCANS; CELL physiology; WNT signal transduction; CELL membranes; GLYCOPROTEINS; GLYCOSAMINOGLYCANS
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-19765-y