Further insight into the roles of the glycans attached to human blood protein C inhibitor
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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; Engström, Åke; Dell, Anne; Schedin-Weiss, Sophia.
In: Biochemical and Biophysical Research Communications, Vol. 403, No. 2, 10.12.2010, p. 198-202.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Further insight into the roles of the glycans attached to human blood protein C inhibitor
AU - Sun, Wei
AU - Parry, Simon
AU - Ubhayasekera, Wimal
AU - Engström, Åke
AU - Dell, Anne
AU - Schedin-Weiss, Sophia
N1 - Keywords: micro-heterogeneity, mass spectrometry, O-glycosylation, protein C inhibitor, serpin
PY - 2010/12/10
Y1 - 2010/12/10
N2 - 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.
AB - 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.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.bbrc.2010.11.005
DO - 10.1016/j.bbrc.2010.11.005
M3 - Journal article
C2 - 21056543
VL - 403
SP - 198
EP - 202
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -
ID: 33863396