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Determining the Effect of Catechins on SOD1 Conformation and Aggregation by Ion Mobility Mass Spectrometry Combined with Optical Spectroscopy

  • Bing Zhao
  • Xiaoyu Zhuang
  • Zifeng Pi
  • Shu Liu
  • Zhiqiang Liu
  • Fengrui Song
Research Article

Abstract

The aggregation of Cu,Zn-superoxide dismutase (SOD1) plays an important role in the etiology of amyotrophic lateral sclerosis (ALS). For the disruption of ALS progression, discovering new drugs or compounds that can prevent SOD1 aggregation is important. In this study, ESI-MS was used to investigate the interaction of catechins and SOD1. The noncovalent complex of catechins that interact with SOD1 was found and retained in the gas phase under native ESI-MS condition. The conformation changes of SOD1 after binding with catechins were also explored via traveling wave ion mobility (IM) spectrometry. Epigallocatechin gallate (EGCG) can stabilize SOD1 conformation against unfolding in three catechins. To further evaluate the efficacy of EGCG, we monitored the fluorescence changes of dimer E2,E2,-SOD1(apo-SOD1, E:empty) with and without ligands under denaturation conditions, and found that EGCG can inhibit apo-SOD1 aggregation. In addition, the circular dichroism spectra of the samples showed that EGCG can decrease the β-sheet content of SOD1, which can produce aggregates. These results indicated that orthogonal separation dimension in the gas-phase IM coupled with ESI-MS (ESI-IM-MS) can potentially provide insight into the interaction between SOD1 and small molecules. The advantage is that it dramatically decreases the analysis time. Meantime, optical spectroscopy techniques can be used to confirm ESI-IM-MS results.

Graphical Abstract

Keywords

Superoxide dismutase Conformation interactions Ion mobility mass spectrometry Catechin 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 21673219 and 81530094).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interest.

Supplementary material

13361_2017_1864_MOESM1_ESM.docx (924 kb)
ESM 1 (DOCX 924 kb)

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Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.National Center of Mass Spectrometry in Changchun & Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunChina
  2. 2.University of Science and Technology of ChinaHefeiChina

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