Large-Scale Qualitative and Quantitative Top-Down Proteomics Using Capillary Zone Electrophoresis-Electrospray Ionization-Tandem Mass Spectrometry with Nanograms of Proteome Samples

Lubeckyj, Rachele A.; Basharat, Abdul Rehman; Shen, Xiaojing; Liu, Xiaowen; Sun, Liangliang

doi:10.1007/s13361-019-02167-w

Cited by 72Advanced Proteomics Techniques and ApplicationsMass Spectrometry Techniques and ApplicationsMicrofluidic and Capillary Electrophoresis Applications

Large-Scale Qualitative and Quantitative Top-Down Proteomics Using Capillary Zone Electrophoresis-Electrospray Ionization-Tandem Mass Spectrometry with Nanograms of Proteome Samples

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Lubeckyj, Rachele A., Basharat, Abdul Rehman, Shen, Xiaojing, Liu, Xiaowen, Sun, Liangliang·2019·Journal of the American Society for Mass Spectrometry

DOI 10.1007/s13361-019-02167-wPMC PMC6675661

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Abstract

Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry (CZE-ESI-MS/MS) has attracted attention recently for top-down proteomics because it can achieve highly efficient separation and very sensitive detection of proteins. However, separation window and sample loading volume of CZE need to be boosted for a better proteome coverage using CZE-MS/MS. Here, we present an improved CZE-MS/MS system that achieved a 180-min separation window and a 2-μL sample loading volume for top-down characterization of protein mixtures. The system obtained highly efficient separation of proteins with nearly one million theoretical plates for myoglobin and enabled baseline separation of three different proteoforms of myoglobin. The CZE-MS/MS system identified 797 ± 21 proteoforms and 258 ± 7 proteins (n = 2) from an Escherichia coli (E. coli) proteome sample in a single run with only 250 ng of proteins injected. The system still identified 449 ± 40 proteoforms and 173 ± 6 proteins (n = 2) from the E. coli sample when only 25 ng of proteins were injected per run. Single-shot CZE-MS/MS analyses of zebrafish brain cerebellum (Cb) and optic tectum (Teo) regions identified 1730 ± 196 proteoforms (n = 3) and 2024 ± 255 proteoforms (n = 3), respectively, with only 500-ng proteins loaded per run. Label-free quantitative top-down proteomics of zebrafish brain Cb and Teo regions revealed significant differences between Cb and Teo regarding the proteoform abundance. Over 700 proteoforms from 131 proteins had significantly higher abundance in Cb compared to Teo, and these proteins were highly enriched in several biological processes, including muscle contraction, glycolytic process, and mesenchyme migration. Graphical Abstract.

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A prior CZE-MS study identified about 800 proteoforms from only 250 ng of proteins.
“A recent study using CZE-MS indicated ~800 proteoforms could be identified from only 250 ng of proteins.19”
From Sensitive Top-Down Proteomics Analysis of a Low Number of Mammalian Cells Using a Nanodroplet Sample Processing Platform (2020) · cites this paper as [19]
The quantitative CZE-MS approach revealed that proteoform abundance differs significantly in different regions of the zebrafish brain.
“This quantitative approach revealed that the abundance of proteoforms differs significantly in different regions of the zebrafish brain.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [135]
Label-free CZE-MS quantified thousands of proteoforms from zebrafish brain.
“In a TDMS study, Lubeckyj et al. demonstrated a label-free strategy for the quantification of thousands of proteoforms from zebrafish brain using CZE-MS135.”
From Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research (2019) · cites this paper as [135]

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Authors: Lubeckyj, R. A., Basharat, A. R., Shen, X., Liu, X., & Sun, L.
Affiliations: Michigan State University (US)
Indiana University – Purdue University Indianapolis (US)
Indiana University Indianapolis (US)
Corresponding author: Sun, Liangliang
ORCID: Basharat, Abdul Rehman
Shen, Xiaojing
Liu, Xiaowen
Sun, Liangliang
Venue: Journal of the American Society for Mass Spectrometry
Publisher: American Chemical Society (ACS)
Published: 2019-04-09
Volume: 30
Issue: 8
Pages: 1435-1445
ISSN: 1044-0305 (ISSN-L)
DOI: 10.1007/s13361-019-02167-w
PMC: PMC6675661
OpenAlex: W2938894406
Cited by: 72
References: 40
Citations by year: 2026: 11 · 2025: 11 · 2024: 11 · 2023: 4 · 2022: 10 · 2021: 12 · 2020: 10 · 2019: 3
FWCI: 3.48
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Journal of the American Society for Mass Spectrometry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
IUScholarWorks (Indiana University) (submittedVersion)
Purdue University Indianapolis (Indiana University) (submittedVersion)
PMC
Funders: National Institute of General Medical Sciences (R01GM118470, R01GM125991)
Topics: Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
Keywords: top-down proteomics, capillary zone electrophoresis, proteoforms, myoglobin, Escherichia coli proteome, label-free quantitative proteomics
MeSH terms: Animals, Cattle, Escherichia coli, Horses, Myoglobin, Proteins, Electrophoresis, Capillary, Proteome, Spectrometry, Mass, Electrospray Ionization, Escherichia coli Proteins, Proteomics, Tandem Mass Spectrometry

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Large-Scale Qualitative and Quantitative Top-Down Proteomics Using Capillary Zone Electrophoresis-Electrospray Ionization-Tandem Mass Spectrometry with Nanograms of Proteome Samples

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