Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of α-Synuclein Protein

Piriya Wongkongkathep, Jong Yoon Han, Tae Su Choi, Sheng Yin, Hugh I. Kim, Joseph A. Loo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS 3 ), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)1870-1880
Number of pages11
JournalJournal of the American Society for Mass Spectrometry
Volume29
Issue number9
DOIs
Publication statusPublished - 2018 Sep 1

Fingerprint

Synucleins
Manganese
Cobalt
Mass spectrometry
Mass Spectrometry
Carrier Proteins
Metals
Intrinsically Disordered Proteins
Ions
Proteins
Ligands
Cyclotrons
Fourier Analysis
Heavy Metals
Cyclotron resonance
Protein Binding
Parkinson Disease
Binding Sites
Electrons
Fourier transforms

Keywords

  • Electron capture dissociation
  • Electrospray ionization
  • Metal binding
  • Native mass spectrometry
  • Protein-ligand complex
  • Top-down mass spectrometry
  • α-Synuclein

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy

Cite this

Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of α-Synuclein Protein. / Wongkongkathep, Piriya; Han, Jong Yoon; Choi, Tae Su; Yin, Sheng; Kim, Hugh I.; Loo, Joseph A.

In: Journal of the American Society for Mass Spectrometry, Vol. 29, No. 9, 01.09.2018, p. 1870-1880.

Research output: Contribution to journalArticle

@article{98d63fe076ba41ee8c2f5fb8690864ae,
title = "Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of α-Synuclein Protein",
abstract = "Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS 3 ), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins. [Figure not available: see fulltext.].",
keywords = "Electron capture dissociation, Electrospray ionization, Metal binding, Native mass spectrometry, Protein-ligand complex, Top-down mass spectrometry, α-Synuclein",
author = "Piriya Wongkongkathep and Han, {Jong Yoon} and Choi, {Tae Su} and Sheng Yin and Kim, {Hugh I.} and Loo, {Joseph A.}",
year = "2018",
month = "9",
day = "1",
doi = "10.1007/s13361-018-2002-2",
language = "English",
volume = "29",
pages = "1870--1880",
journal = "Journal of the American Society for Mass Spectrometry",
issn = "1044-0305",
publisher = "Springer New York",
number = "9",

}

TY - JOUR

T1 - Native Top-Down Mass Spectrometry and Ion Mobility MS for Characterizing the Cobalt and Manganese Metal Binding of α-Synuclein Protein

AU - Wongkongkathep, Piriya

AU - Han, Jong Yoon

AU - Choi, Tae Su

AU - Yin, Sheng

AU - Kim, Hugh I.

AU - Loo, Joseph A.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS 3 ), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins. [Figure not available: see fulltext.].

AB - Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field of protein science due to limited capabilities to obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized to obtain structural features of protein-ligand binding for the Parkinson’s disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding of heavy metals has been implicated in the accelerated formation of αSyn aggregation. Using high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry, native top-down MS with various fragmentation methods, including electron capture dissociation (ECD), collisional activated dissociation (CAD), and multistage tandem MS (MS 3 ), deduced the binding sites of cobalt and manganese to the C-terminal region of the protein. Ion mobility MS (IM-MS) revealed a collapse toward compacted states of αSyn upon metal binding. The combination of native top-down MS and IM-MS provides structural information of protein-ligand interactions for intrinsically disordered proteins. [Figure not available: see fulltext.].

KW - Electron capture dissociation

KW - Electrospray ionization

KW - Metal binding

KW - Native mass spectrometry

KW - Protein-ligand complex

KW - Top-down mass spectrometry

KW - α-Synuclein

UR - http://www.scopus.com/inward/record.url?scp=85051446010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051446010&partnerID=8YFLogxK

U2 - 10.1007/s13361-018-2002-2

DO - 10.1007/s13361-018-2002-2

M3 - Article

C2 - 29951842

AN - SCOPUS:85051446010

VL - 29

SP - 1870

EP - 1880

JO - Journal of the American Society for Mass Spectrometry

JF - Journal of the American Society for Mass Spectrometry

SN - 1044-0305

IS - 9

ER -