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

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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; Logan, Derek T.

I: Journal of Biological Chemistry, Vol. 290, Nr. 38, 2015, s. 22991-23008.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Awad, Wael ; Adamczyk, Barbara ; Örnros, Jessica ; Karlsson, Niclas G ; Mani, Katrin ; Logan, Derek T. / Structural aspects of N-glycosylations and the C-terminal region in human glypican-1. I: Journal of Biological Chemistry. 2015 ; Vol. 290, Nr. 38. s. 22991-23008.

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TY - JOUR

T1 - Structural aspects of N-glycosylations and the C-terminal region in human glypican-1.

AU - Awad, Wael

AU - Adamczyk, Barbara

AU - Örnros, Jessica

AU - Karlsson, Niclas G

AU - Mani, Katrin

AU - Logan, Derek T

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M115.660878

DO - 10.1074/jbc.M115.660878

M3 - Article

VL - 290

SP - 22991

EP - 23008

JO - Journal of Biological Chemistry

T2 - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 38

ER -