Glycan characterization of pregnancy-specific glycoprotein 1 and its identification as a novel Galectin-1 ligand

TY - JOUR

T1 - Glycan characterization of pregnancy-specific glycoprotein 1 and its identification as a novel Galectin-1 ligand

AU - Mendoza, Mirian

AU - Lu, Dongli

AU - Ballesteros, Angela

AU - Blois, Sandra M

AU - Abernathy, Kelsey

AU - Feng, Chiguang

AU - Dimitroff, Charles J

AU - Zmuda, Jonathan

AU - Panico, Maria

AU - Dell, Anne

AU - Vasta, Gerardo R

AU - Haslam, Stuart M

AU - Dveksler, Gabriela

N1 - Published by Oxford University Press 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.

PY - 2020/10/21

Y1 - 2020/10/21

N2 - Pregnancy-specific beta 1 glycoprotein (PSG1) is secreted from trophoblast cells of the human placenta in increasing concentrations as pregnancy progresses, becoming one of the most abundant proteins in maternal serum in the third trimester. PSG1 has seven potential N-linked glycosylation sites across its four domains. We carried out glycomic and glycoproteomic studies to characterize the glycan composition of PSG1 purified from serum of pregnant women and identified the presence of complex N-glycans containing poly LacNAc epitopes with α2,3 sialyation at four sites. Using different techniques, we explored whether PSG1 can bind to galectin-1 (Gal-1) as these two proteins were previously shown to participate in processes required for a successful pregnancy. We confirmed that PSG1 binds to Gal-1 in a carbohydrate-dependent manner with an affinity of the interaction of 0.13 μM. In addition, we determined that out of the three N-glycosylation-carrying domains, only the N and A2 domains of recombinant PSG1 interact with Gal-1. Lastly, we observed that the interaction between PSG1 and Gal-1 protects this lectin from oxidative inactivation and that PSG1 competes the ability of Gal-1 to bind to some but not all of its glycoprotein ligands.

AB - Pregnancy-specific beta 1 glycoprotein (PSG1) is secreted from trophoblast cells of the human placenta in increasing concentrations as pregnancy progresses, becoming one of the most abundant proteins in maternal serum in the third trimester. PSG1 has seven potential N-linked glycosylation sites across its four domains. We carried out glycomic and glycoproteomic studies to characterize the glycan composition of PSG1 purified from serum of pregnant women and identified the presence of complex N-glycans containing poly LacNAc epitopes with α2,3 sialyation at four sites. Using different techniques, we explored whether PSG1 can bind to galectin-1 (Gal-1) as these two proteins were previously shown to participate in processes required for a successful pregnancy. We confirmed that PSG1 binds to Gal-1 in a carbohydrate-dependent manner with an affinity of the interaction of 0.13 μM. In addition, we determined that out of the three N-glycosylation-carrying domains, only the N and A2 domains of recombinant PSG1 interact with Gal-1. Lastly, we observed that the interaction between PSG1 and Gal-1 protects this lectin from oxidative inactivation and that PSG1 competes the ability of Gal-1 to bind to some but not all of its glycoprotein ligands.

U2 - 10.1093/glycob/cwaa034

DO - 10.1093/glycob/cwaa034

M3 - SCORING: Journal article

C2 - 32280962

VL - 30

SP - 895

EP - 909

JO - GLYCOBIOLOGY

JF - GLYCOBIOLOGY

SN - 0959-6658

IS - 11

ER -