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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Wael Awad
  • Barbara Adamczyk
  • Jessica Örnros
  • Niclas G Karlsson
  • Katrin Mani
  • Derek T Logan
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)22991-23008
JournalJournal of Biological Chemistry
Volume290
Issue number38
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes