Skip to main content

Applications of Mass Spectrometry to the Study of Protein Aggregation

  • Protocol
  • First Online:
Insoluble Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1258))

Abstract

Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles. Nowadays mass spectrometry-based approaches play a pivotal role in both detection and characterization of proteins. Here we describe two applications to study insoluble proteins: (a) hydrogen/deuterium exchange combined with mass spectrometry to analyze structural properties of amyloid fibrils and (b) the screening for inhibitors of the aggregation process by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Beveridge R, Chappuis Q, Macphee C et al (2013) Mass spectrometry methods for intrinsically disordered proteins. Analyst 138:32–42

    Article  CAS  PubMed  Google Scholar 

  2. Grasso G (2011) The use of mass spectrometry to study amyloid-β peptides. Mass Spectrom Rev 30:347–365

    Article  CAS  PubMed  Google Scholar 

  3. Stoeckli M, Knochenmuss R, McCombie G et al (2006) MALDI MS imaging of amyloid. Methods Enzymol 412:94–106

    Article  CAS  PubMed  Google Scholar 

  4. Woods L, Radford SE, Ashcroft E (2013) Advances in ion mobility spectrometry-mass spectrometry reveal key insights into amyloid assembly. Biochim Biophys Acta 1834:1257–1268

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Lu X, Wintrode PL, Surewicz WL (2007) Beta-sheet core of human prion protein amyloid fibrils as determined by hydrogen/deuterium exchange. Proc Natl Acad Sci U S A 104:1510–1515

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Carulla N, Zhou M, Arimon M et al (2009) Experimental characterization of disordered and ordered aggregates populated during the process of amyloid fibril formation. Proc Natl Acad Sci U S A 106:7828–7833

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Cravello L, Lascoux D, Forest E (2003) Use of different proteases working in acidic conditions to improve sequence coverage and resolution in hydrogen/deuterium exchange of large proteins. Rapid Commun Mass Spectrom 17:2387–2393

    Article  CAS  PubMed  Google Scholar 

  8. Qi W, Zhang A, Patel D et al (2008) Simultaneous monitoring of peptide aggregate distributions, structure, and kinetics using amide hydrogen exchange: application to Abeta(1-40) fibrillogenesis. Biotechnol Bioeng 100:1214–1227

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Zhang Z, Smith DL (1993) Determination of amide hydrogen exchange by mass spectrometry: a new tool for protein structure elucidation. Protein Sci 2:522–531

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Nerelius C, Gustafsson M, Nordling K et al (2009) Anti-amyloid activity of the C-terminal domain of proSP-C against amyloid beta-peptide and medin. Biochemistry 48:3778–3786

    Article  CAS  PubMed  Google Scholar 

  11. Skribanek Z, Baláspiri L, Mák M (2001) Interaction between synthetic amyloid-β-peptide (1-40) and its aggregation inhibitors studied by electrospray ionization mass spectrometry. J Mass Spectrom 36:1226–1229

    Article  CAS  PubMed  Google Scholar 

  12. Cheng X, van Breemen RB (2005) Mass spectrometry-based screening for inhibitors of β-amyloid protein aggregation. Anal Chem 77:7012–7015

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Necula M, Kayed R, Milton S (2007) Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. J Biol Chem 282:10311–10324

    Article  CAS  PubMed  Google Scholar 

  14. Bartolini M, Naldi M, Fiori J et al (2011) Kinetic characterization of amyloid-beta 1-42 aggregation with a multimethodological approach. Anal Biochem 414:215–225

    Article  CAS  PubMed  Google Scholar 

  15. Fiori J, Naldi M, Bartolini M et al (2012) Disclosure of a fundamental clue for the elucidation of the myricetin mechanism of action as amyloid aggregation inhibitor by mass spectrometry. Electrophoresis 33:3380–3386

    Article  CAS  PubMed  Google Scholar 

  16. Del Mar C, Greenbaum E, Mayne L et al (2005) Structure and properties of alpha-synuclein and other amyloids determined at the amino acid level. Proc Natl Acad Sci U S A 102:15477–15482

    Article  PubMed Central  PubMed  Google Scholar 

  17. Damo SM, Phillips AH, Young AL et al (2010) Probing the conformation of a prion protein fibril with hydrogen exchange. J Biol Chem 285:32303–32311

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. French KC, Makhatadze GI (2012) Core sequence of PAPf39 amyloid fibrils and mechanism of pH-dependent fibril formation: the role of monomer conformation. Biochemistry 51:10127–10136

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Bartolini M, Bertucci C, Bolognesi ML et al (2007) Insight into the kinetic of amyloid beta (1-42) peptide self-aggregation: elucidation of inhibitors’ mechanism of action. Chembiochem 8:2152–2161

    Article  CAS  PubMed  Google Scholar 

  20. Bartolini M, Bertucci C, Cavrini V et al (2003) beta-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies. Biochem Pharmacol 65:407–416

    Article  CAS  PubMed  Google Scholar 

  21. Zovo K, Helk E, Karafin A et al (2010) Label-free high-throughput screening assay for inhibitors of Alzheimer’s amyloid-β peptide aggregation based on MALDI MS. Anal Chem 82:8558–8565

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sílvia Bronsoms .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Bronsoms, S., Trejo, S.A. (2015). Applications of Mass Spectrometry to the Study of Protein Aggregation. In: García-Fruitós, E. (eds) Insoluble Proteins. Methods in Molecular Biology, vol 1258. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2205-5_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2205-5_19

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2204-8

  • Online ISBN: 978-1-4939-2205-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics