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

17 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

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

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