Advanced

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

Awad, Wael; Adamczyk, Barbara; Örnros, Jessica; Karlsson, Niclas G; Mani, Katrin LU and Logan, Derek T (2015) In Journal of Biological Chemistry 290(38). p.22991-23008
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
290
issue
38
pages
22991 - 23008
publisher
ASBMB
external identifiers
  • pmid:26203194
  • wos:000361685500012
  • scopus:84942896464
ISSN
1083-351X
DOI
10.1074/jbc.M115.660878
language
English
LU publication?
yes
id
b76e1731-ec4b-407e-97c1-d96d861ced71 (old id 7721248)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26203194?dopt=Abstract
date added to LUP
2015-08-10 16:28:51
date last changed
2017-01-01 03:04:38
@article{b76e1731-ec4b-407e-97c1-d96d861ced71,
  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.},
  author       = {Awad, Wael and Adamczyk, Barbara and Örnros, Jessica and Karlsson, Niclas G and Mani, Katrin and Logan, Derek T},
  issn         = {1083-351X},
  language     = {eng},
  number       = {38},
  pages        = {22991--23008},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Structural aspects of N-glycosylations and the C-terminal region in human glypican-1.},
  url          = {http://dx.doi.org/10.1074/jbc.M115.660878},
  volume       = {290},
  year         = {2015},
}