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:
https://lup.lub.lu.se/record/7721248
- author
- Awad, Wael
; Adamczyk, Barbara
; Örnros, Jessica
; Karlsson, Niclas G
; Mani, Katrin
LU
and Logan, Derek T
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 290
- issue
- 38
- pages
- 22991 - 23008
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:26203194
- wos:000361685500012
- scopus:84942896464
- pmid:26203194
- 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
- 2016-04-01 09:52:48
- date last changed
- 2023-08-30 12:06:21
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M115.660878}},
volume = {{290}},
year = {{2015}},
}