Structural aspects of N-glycosylations and the C-terminal region in human glypican-1.
Research output: Contribution to journal › Article
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.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 2015|