An affinity chromatography and glycoproteomics workflow to profile the chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in the placenta and in cancer.
cancer
chondroitin sulfate
glycopeptides
mass spectrometry
proteoglycans
Journal
Glycobiology
ISSN: 1460-2423
Titre abrégé: Glycobiology
Pays: England
ID NLM: 9104124
Informations de publication
Date de publication:
09 12 2020
09 12 2020
Historique:
received:
20
02
2020
revised:
20
03
2020
accepted:
22
04
2020
pubmed:
28
4
2020
medline:
3
11
2021
entrez:
28
4
2020
Statut:
ppublish
Résumé
Chondroitin sulfate (CS) is the placental receptor for the VAR2CSA malaria protein, expressed at the surface of infected erythrocytes during Plasmodium falciparum infection. Infected cells adhere to syncytiotrophoblasts or get trapped within the intervillous space by binding to a determinant in a 4-O-sulfated CS chains. However, the exact structure of these glycan sequences remains unclear. VAR2CSA-reactive CS is also expressed by tumor cells, making it an attractive target for cancer diagnosis and therapeutics. The identities of the proteoglycans carrying these modifications in placental and cancer tissues remain poorly characterized. This information is clinically relevant since presentation of the glycan chains may be mediated by novel core proteins or by a limited subset of established proteoglycans. To address this question, VAR2CSA-binding proteoglycans were affinity-purified from the human placenta, tumor tissues and cancer cells and analyzed through a specialized glycoproteomics workflow. We show that VAR2CSA-reactive CS chains associate with a heterogenous group of proteoglycans, including novel core proteins. Additionally, this work demonstrates how affinity purification in combination with glycoproteomics analysis can facilitate the characterization of CSPGs with distinct CS epitopes. A similar workflow can be applied to investigate the interaction of CSPGs with other CS binding lectins as well.
Identifiants
pubmed: 32337544
pii: 5825273
doi: 10.1093/glycob/cwaa039
pmc: PMC7724742
doi:
Substances chimiques
Antigens, Protozoan
0
Chondroitin Sulfate Proteoglycans
0
VAR2CSA protein, Plasmodium falciparum
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
989-1002Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL131474
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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