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Further insight into the roles of the glycans attached to human blood protein C inhibitor

Sun, Wei; Parry, Simon; Ubhayasekera, Wimal LU ; Engstrom, Ake; Dell, Anne and Schedin-Weiss, Sophia (2010) In Biochemical and Biophysical Research Communications 403(2). p.198-202
Abstract
Protein C inhibitor (PCI) is a 57-kDa glycoprotein that exists in many tissues and secretions in human. As a member of the serpin superfamily of proteins it displays unusually broad protease specificity. PCI is implicated in the regulation of a wide range of processes, including blood coagulation, fertilization, prevention of tumors and pathogen defence. It has been reported that PCI isolated from human blood plasma is highly heterogeneous, and that this heterogeneity is caused by differences in N-glycan structures, N-glycosylation occupancy, and the presence of two forms that differ by the presence or absence of 6 amino acids at the amino-terminus. In this study we have verified that such heterogeneity exists in PCI purified from single... (More)
Protein C inhibitor (PCI) is a 57-kDa glycoprotein that exists in many tissues and secretions in human. As a member of the serpin superfamily of proteins it displays unusually broad protease specificity. PCI is implicated in the regulation of a wide range of processes, including blood coagulation, fertilization, prevention of tumors and pathogen defence. It has been reported that PCI isolated from human blood plasma is highly heterogeneous, and that this heterogeneity is caused by differences in N-glycan structures, N-glycosylation occupancy, and the presence of two forms that differ by the presence or absence of 6 amino acids at the amino-terminus. In this study we have verified that such heterogeneity exists in PCI purified from single individuals, and that individuals of two different ethnicities possess a similar PCI pattern, verifying that the micro-heterogeneity is conserved among humans. Furthermore, we have provided experimental evidence that PCI in both individuals is O-glycosylated on Thr20 with a core type 1 O-glycan, which is mostly NeuAcGalGalNAc. Modeling suggested that the O-glycan attachment site is located in proximity to several ligand-binding sites of the inhibitor. (C) 2010 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Micro-heterogeneity, Mass spectrometry, O-glycosylation, Protein C, inhibitor, Serpin
in
Biochemical and Biophysical Research Communications
volume
403
issue
2
pages
198 - 202
publisher
Elsevier
external identifiers
  • wos:000285534500008
  • scopus:78649907006
ISSN
1090-2104
DOI
10.1016/j.bbrc.2010.11.005
language
English
LU publication?
yes
id
c429e75c-7988-4fff-9be2-62700a660d05 (old id 1831246)
date added to LUP
2011-03-02 11:25:53
date last changed
2018-05-29 12:32:16
@article{c429e75c-7988-4fff-9be2-62700a660d05,
  abstract     = {Protein C inhibitor (PCI) is a 57-kDa glycoprotein that exists in many tissues and secretions in human. As a member of the serpin superfamily of proteins it displays unusually broad protease specificity. PCI is implicated in the regulation of a wide range of processes, including blood coagulation, fertilization, prevention of tumors and pathogen defence. It has been reported that PCI isolated from human blood plasma is highly heterogeneous, and that this heterogeneity is caused by differences in N-glycan structures, N-glycosylation occupancy, and the presence of two forms that differ by the presence or absence of 6 amino acids at the amino-terminus. In this study we have verified that such heterogeneity exists in PCI purified from single individuals, and that individuals of two different ethnicities possess a similar PCI pattern, verifying that the micro-heterogeneity is conserved among humans. Furthermore, we have provided experimental evidence that PCI in both individuals is O-glycosylated on Thr20 with a core type 1 O-glycan, which is mostly NeuAcGalGalNAc. Modeling suggested that the O-glycan attachment site is located in proximity to several ligand-binding sites of the inhibitor. (C) 2010 Elsevier Inc. All rights reserved.},
  author       = {Sun, Wei and Parry, Simon and Ubhayasekera, Wimal and Engstrom, Ake and Dell, Anne and Schedin-Weiss, Sophia},
  issn         = {1090-2104},
  keyword      = {Micro-heterogeneity,Mass spectrometry,O-glycosylation,Protein C,inhibitor,Serpin},
  language     = {eng},
  number       = {2},
  pages        = {198--202},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Further insight into the roles of the glycans attached to human blood protein C inhibitor},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2010.11.005},
  volume       = {403},
  year         = {2010},
}