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

Summary, in English

Glypicans are multifunctional cell surface proteoglycans involved in several important cellular signalling pathways. Glypican-1 (Gpc1) is the predominant heparan sulphate (HS) proteoglycan in the developing and adult human brain. The two N-linked glycans and the C-terminal domain that attaches 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 the N-glycans and the C-terminus, and also the topology of Gpc1 with respect to the membrane. The C-terminus 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 orthologues towards the membrane, where it may interact with signalling molecules and/or membrane receptors on the cell surface, or even the enzymes involved in HS substitution in the Golgi apparatus Furthermore, the N-glycans are shown to extend the protein stability and lifetime by protection against proteolysis and aggregation.

• Author: Wael Awad; Barbara Adamczyk; Jessica Örnros; Niclas G Karlsson; Katrin Mani; Derek T Logan
• Department/s: Glycobiology; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2015
• Language: English
• Pages: 22991-23008
• Publication/Series: Journal of Biological Chemistry
• Volume: 290
• Issue: 38
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26203194?dopt=Abstract; http://dx.doi.org/10.1074/jbc.M115.660878
• Document type: Journal article
• Publisher: American Society for Biochemistry and Molecular Biology
• Topic: Cell and Molecular Biology
• Status: Published
• Research group: Glycobiology
• ISBN/ISSN/Other: ISSN: 1083-351X