Structural aspects of N-glycosylations and the C-terminal region in human glypican-1

Wael Awad, Barbara Adamczyk, Jessica Örnros, Niclas G. Karlsson, Katrin Mani, Derek T. Logan

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

Glypicans are multifunctional cell surface proteoglycans involved in several important cellular signaling pathways. Glypican-1 (Gpc1) is the predominant heparan sulfate proteoglycan in the developing and adult human brain. The two N-linked glycans and the C-terminal domain that attach the core protein to the cell membrane are not resolved in the Gpc1 crystal structure. Therefore, we have studied Gpc1 using crystallography, small angle x-ray scattering, and chromatographic approaches to elucidate the composition, structure, and function of theN-glycans and theCterminus and also the topology of Gpc1 with respect to the membrane. TheCterminus is shown to be highly flexible in solution, but it orients the core protein transverse to the membrane, directing a surface evolutionarily conserved in Gpc1 orthologs toward the membrane, where it may interact with signaling molecules and/or membrane receptors on the cell surface, or even the enzymes involved in heparan sulfate substitution in the Golgi apparatus. Furthermore, the N-glycans are shown to extend the protein stability and lifetime by protection against proteolysis and aggregation.

Original languageEnglish
Pages (from-to)22991-23008
Number of pages18
JournalJournal of Biological Chemistry
Volume290
Issue number38
DOIs
Publication statusPublished - 18 Sep 2015
Externally publishedYes

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