Identification of potential sialic acid binding proteins on cell membranes by proximity chemical labeling

Qiongyu Li, Yixuan Xie, Gege Xu, Carlito B Lebrilla

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The cell membrane contains a highly interactive glycan surface on a scaffold of proteins and lipids. Sialic acids are negatively charged monosaccharides, and the proteins that bind to sialic acids play an important role in maintaining the integrity and collective functions of this interactive space. Sialic acid binding proteins are not readily identified and have nearly all been discovered empirically. In this research, we developed a proximity labeling method to characterize proteins with oxidation by localized radicals produced in situ. The sites of oxidation were identified and quantified using a standard proteomic workflow. In this method, a clickable probe was synthesized and attached to modified sialic acids on the cell membrane, which functioned as a catalyst for the localized formation of radicals from hydrogen peroxide. The proteins in the sialic acid environment were labeled through amino acid oxidation, and were categorized into three groups including sialylated proteins, non-sialylated proteins with transmembrane domains, and proteins that are associated with the membrane with neither sialylated nor transmembrane domains. The analysis of the last group of proteins showed that they were associated with binding functions including carbohydrate binding, anion binding, and cation binding, thereby revealing the nature of the sialic acid-protein interaction. This new tool identified potential sialic acid-binding proteins in the extracellular space and proteins that were organized around sialylated glycans in cells.

Original languageEnglish (US)
Pages (from-to)6199-6209
Number of pages11
JournalChemical Science
Volume10
Issue number24
DOIs
StatePublished - Jan 1 2019

Fingerprint

N-Acetylneuraminic Acid
Cell membranes
Labeling
Carrier Proteins
Sialic Acids
Proteins
Oxidation
Polysaccharides
Monosaccharides
Scaffolds
Hydrogen Peroxide
Anions
Cations
Carbohydrates
Membranes
Lipids
Amino Acids
Catalysts

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Identification of potential sialic acid binding proteins on cell membranes by proximity chemical labeling. / Li, Qiongyu; Xie, Yixuan; Xu, Gege; Lebrilla, Carlito B.

In: Chemical Science, Vol. 10, No. 24, 01.01.2019, p. 6199-6209.

Research output: Contribution to journalArticle

Li, Qiongyu ; Xie, Yixuan ; Xu, Gege ; Lebrilla, Carlito B. / Identification of potential sialic acid binding proteins on cell membranes by proximity chemical labeling. In: Chemical Science. 2019 ; Vol. 10, No. 24. pp. 6199-6209.
@article{918c8dc7c31049c6929b05f064f20943,
title = "Identification of potential sialic acid binding proteins on cell membranes by proximity chemical labeling",
abstract = "The cell membrane contains a highly interactive glycan surface on a scaffold of proteins and lipids. Sialic acids are negatively charged monosaccharides, and the proteins that bind to sialic acids play an important role in maintaining the integrity and collective functions of this interactive space. Sialic acid binding proteins are not readily identified and have nearly all been discovered empirically. In this research, we developed a proximity labeling method to characterize proteins with oxidation by localized radicals produced in situ. The sites of oxidation were identified and quantified using a standard proteomic workflow. In this method, a clickable probe was synthesized and attached to modified sialic acids on the cell membrane, which functioned as a catalyst for the localized formation of radicals from hydrogen peroxide. The proteins in the sialic acid environment were labeled through amino acid oxidation, and were categorized into three groups including sialylated proteins, non-sialylated proteins with transmembrane domains, and proteins that are associated with the membrane with neither sialylated nor transmembrane domains. The analysis of the last group of proteins showed that they were associated with binding functions including carbohydrate binding, anion binding, and cation binding, thereby revealing the nature of the sialic acid-protein interaction. This new tool identified potential sialic acid-binding proteins in the extracellular space and proteins that were organized around sialylated glycans in cells.",
author = "Qiongyu Li and Yixuan Xie and Gege Xu and Lebrilla, {Carlito B}",
year = "2019",
month = "1",
day = "1",
doi = "10.1039/c9sc01360a",
language = "English (US)",
volume = "10",
pages = "6199--6209",
journal = "Chemical Science",
issn = "2041-6520",
publisher = "Royal Society of Chemistry",
number = "24",

}

TY - JOUR

T1 - Identification of potential sialic acid binding proteins on cell membranes by proximity chemical labeling

AU - Li, Qiongyu

AU - Xie, Yixuan

AU - Xu, Gege

AU - Lebrilla, Carlito B

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The cell membrane contains a highly interactive glycan surface on a scaffold of proteins and lipids. Sialic acids are negatively charged monosaccharides, and the proteins that bind to sialic acids play an important role in maintaining the integrity and collective functions of this interactive space. Sialic acid binding proteins are not readily identified and have nearly all been discovered empirically. In this research, we developed a proximity labeling method to characterize proteins with oxidation by localized radicals produced in situ. The sites of oxidation were identified and quantified using a standard proteomic workflow. In this method, a clickable probe was synthesized and attached to modified sialic acids on the cell membrane, which functioned as a catalyst for the localized formation of radicals from hydrogen peroxide. The proteins in the sialic acid environment were labeled through amino acid oxidation, and were categorized into three groups including sialylated proteins, non-sialylated proteins with transmembrane domains, and proteins that are associated with the membrane with neither sialylated nor transmembrane domains. The analysis of the last group of proteins showed that they were associated with binding functions including carbohydrate binding, anion binding, and cation binding, thereby revealing the nature of the sialic acid-protein interaction. This new tool identified potential sialic acid-binding proteins in the extracellular space and proteins that were organized around sialylated glycans in cells.

AB - The cell membrane contains a highly interactive glycan surface on a scaffold of proteins and lipids. Sialic acids are negatively charged monosaccharides, and the proteins that bind to sialic acids play an important role in maintaining the integrity and collective functions of this interactive space. Sialic acid binding proteins are not readily identified and have nearly all been discovered empirically. In this research, we developed a proximity labeling method to characterize proteins with oxidation by localized radicals produced in situ. The sites of oxidation were identified and quantified using a standard proteomic workflow. In this method, a clickable probe was synthesized and attached to modified sialic acids on the cell membrane, which functioned as a catalyst for the localized formation of radicals from hydrogen peroxide. The proteins in the sialic acid environment were labeled through amino acid oxidation, and were categorized into three groups including sialylated proteins, non-sialylated proteins with transmembrane domains, and proteins that are associated with the membrane with neither sialylated nor transmembrane domains. The analysis of the last group of proteins showed that they were associated with binding functions including carbohydrate binding, anion binding, and cation binding, thereby revealing the nature of the sialic acid-protein interaction. This new tool identified potential sialic acid-binding proteins in the extracellular space and proteins that were organized around sialylated glycans in cells.

UR - http://www.scopus.com/inward/record.url?scp=85067668372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067668372&partnerID=8YFLogxK

U2 - 10.1039/c9sc01360a

DO - 10.1039/c9sc01360a

M3 - Article

AN - SCOPUS:85067668372

VL - 10

SP - 6199

EP - 6209

JO - Chemical Science

JF - Chemical Science

SN - 2041-6520

IS - 24

ER -