Site-specific glycoproteomic characterization of ES-62: the major secreted product of the parasitic worm Acanthocheilonema viteae

Simon J North, Kwamina Botchway, James Doonan, Felicity E Lumb, Anne Dell, William Harnett, Stuart M Haslam

Research output: Contribution to journalArticle

Abstract

ES-62 is the major secreted product of the parasitic filarial nematode Acanthocheilonema viteae and has potent anti-inflammatory activities as a consequence of posttranslational decoration by phosphorylcholine (PC). Previously, we showed that ES-62's PC was attached to N-linked glycans, and using fast atom bombardment mass spectrometry, we characterized the structure of the glycans. However, it was unknown at this time which of ES-62's four potential N-glycosylation sites carries the PC-modified glycans. In the present study, we now employ more advanced analytical tools-nano-flow liquid chromatography with high-definition electrospray mass spectrometry-to show that PC-modified glycans are found at all four potential N-glycosylation sites. Also, our earlier studies showed that up to two PC groups were detected per glycan, and we are now able to characterize N-glycans with up to five PC groups. The number per glycan varies in three of the four glycosylation sites, and in addition, for the first time, we have detected PC on the N-glycan chitobiose core in addition to terminal GlcNAc. Nevertheless, the majority of PC is detected on terminal GlcNAc, enabling it to interact with the cells and molecules of the immune system. Such expression may explain the potent immunomodulatory effects of a molecule that is considered to have significant therapeutic potential in the treatment of certain human allergic and autoimmune conditions.

LanguageEnglish
Pages562-571
Number of pages10
JournalGlycobiology
Volume29
Issue number8
Early online date16 May 2019
DOIs
Publication statusPublished - 30 Aug 2019

Fingerprint

Acanthocheilonema
Phosphorylcholine
Helminths
Polysaccharides
Glycosylation
Mass spectrometry
Fast Atom Bombardment Mass Spectrometry
Molecules
Immune system
Liquid chromatography
Liquid Chromatography
Immune System
Mass Spectrometry
Anti-Inflammatory Agents

Keywords

  • ES-62
  • glycoproteomics
  • mass spectrometry
  • phosphorylcholine

Cite this

North, Simon J ; Botchway, Kwamina ; Doonan, James ; Lumb, Felicity E ; Dell, Anne ; Harnett, William ; Haslam, Stuart M. / Site-specific glycoproteomic characterization of ES-62 : the major secreted product of the parasitic worm Acanthocheilonema viteae. In: Glycobiology. 2019 ; Vol. 29, No. 8. pp. 562-571.
@article{8dc407e16c664aa3b7734cde63e92e27,
title = "Site-specific glycoproteomic characterization of ES-62: the major secreted product of the parasitic worm Acanthocheilonema viteae",
abstract = "ES-62 is the major secreted product of the parasitic filarial nematode Acanthocheilonema viteae and has potent anti-inflammatory activities as a consequence of posttranslational decoration by phosphorylcholine (PC). Previously, we showed that ES-62's PC was attached to N-linked glycans, and using fast atom bombardment mass spectrometry, we characterized the structure of the glycans. However, it was unknown at this time which of ES-62's four potential N-glycosylation sites carries the PC-modified glycans. In the present study, we now employ more advanced analytical tools-nano-flow liquid chromatography with high-definition electrospray mass spectrometry-to show that PC-modified glycans are found at all four potential N-glycosylation sites. Also, our earlier studies showed that up to two PC groups were detected per glycan, and we are now able to characterize N-glycans with up to five PC groups. The number per glycan varies in three of the four glycosylation sites, and in addition, for the first time, we have detected PC on the N-glycan chitobiose core in addition to terminal GlcNAc. Nevertheless, the majority of PC is detected on terminal GlcNAc, enabling it to interact with the cells and molecules of the immune system. Such expression may explain the potent immunomodulatory effects of a molecule that is considered to have significant therapeutic potential in the treatment of certain human allergic and autoimmune conditions.",
keywords = "ES-62, glycoproteomics, mass spectrometry, phosphorylcholine",
author = "North, {Simon J} and Kwamina Botchway and James Doonan and Lumb, {Felicity E} and Anne Dell and William Harnett and Haslam, {Stuart M}",
year = "2019",
month = "8",
day = "30",
doi = "10.1093/glycob/cwz035",
language = "English",
volume = "29",
pages = "562--571",
journal = "Glycobiology",
issn = "0959-6658",
number = "8",

}

Site-specific glycoproteomic characterization of ES-62 : the major secreted product of the parasitic worm Acanthocheilonema viteae. / North, Simon J; Botchway, Kwamina; Doonan, James; Lumb, Felicity E; Dell, Anne; Harnett, William; Haslam, Stuart M.

In: Glycobiology, Vol. 29, No. 8, 30.08.2019, p. 562-571.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Site-specific glycoproteomic characterization of ES-62

T2 - Glycobiology

AU - North, Simon J

AU - Botchway, Kwamina

AU - Doonan, James

AU - Lumb, Felicity E

AU - Dell, Anne

AU - Harnett, William

AU - Haslam, Stuart M

PY - 2019/8/30

Y1 - 2019/8/30

N2 - ES-62 is the major secreted product of the parasitic filarial nematode Acanthocheilonema viteae and has potent anti-inflammatory activities as a consequence of posttranslational decoration by phosphorylcholine (PC). Previously, we showed that ES-62's PC was attached to N-linked glycans, and using fast atom bombardment mass spectrometry, we characterized the structure of the glycans. However, it was unknown at this time which of ES-62's four potential N-glycosylation sites carries the PC-modified glycans. In the present study, we now employ more advanced analytical tools-nano-flow liquid chromatography with high-definition electrospray mass spectrometry-to show that PC-modified glycans are found at all four potential N-glycosylation sites. Also, our earlier studies showed that up to two PC groups were detected per glycan, and we are now able to characterize N-glycans with up to five PC groups. The number per glycan varies in three of the four glycosylation sites, and in addition, for the first time, we have detected PC on the N-glycan chitobiose core in addition to terminal GlcNAc. Nevertheless, the majority of PC is detected on terminal GlcNAc, enabling it to interact with the cells and molecules of the immune system. Such expression may explain the potent immunomodulatory effects of a molecule that is considered to have significant therapeutic potential in the treatment of certain human allergic and autoimmune conditions.

AB - ES-62 is the major secreted product of the parasitic filarial nematode Acanthocheilonema viteae and has potent anti-inflammatory activities as a consequence of posttranslational decoration by phosphorylcholine (PC). Previously, we showed that ES-62's PC was attached to N-linked glycans, and using fast atom bombardment mass spectrometry, we characterized the structure of the glycans. However, it was unknown at this time which of ES-62's four potential N-glycosylation sites carries the PC-modified glycans. In the present study, we now employ more advanced analytical tools-nano-flow liquid chromatography with high-definition electrospray mass spectrometry-to show that PC-modified glycans are found at all four potential N-glycosylation sites. Also, our earlier studies showed that up to two PC groups were detected per glycan, and we are now able to characterize N-glycans with up to five PC groups. The number per glycan varies in three of the four glycosylation sites, and in addition, for the first time, we have detected PC on the N-glycan chitobiose core in addition to terminal GlcNAc. Nevertheless, the majority of PC is detected on terminal GlcNAc, enabling it to interact with the cells and molecules of the immune system. Such expression may explain the potent immunomodulatory effects of a molecule that is considered to have significant therapeutic potential in the treatment of certain human allergic and autoimmune conditions.

KW - ES-62

KW - glycoproteomics

KW - mass spectrometry

KW - phosphorylcholine

UR - http://www.scopus.com/inward/record.url?scp=85070117865&partnerID=8YFLogxK

U2 - 10.1093/glycob/cwz035

DO - 10.1093/glycob/cwz035

M3 - Article

VL - 29

SP - 562

EP - 571

JO - Glycobiology

JF - Glycobiology

SN - 0959-6658

IS - 8

ER -