Hydrogen/deuterium exchange mass spectrometry identifies two highly protected regions in recombinant full-length prion protein amyloid fibrils

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Author(s) Nazabal, Alexis, Hornemann, Simone, Aguzzi, Adriano, Zenobi, Renato
Publication Type Journal Items, Publication Status: Published
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Title Hydrogen/deuterium exchange mass spectrometry identifies two highly protected regions in recombinant full-length prion protein amyloid fibrils
Author(s) Nazabal, Alexis
Hornemann, Simone
Aguzzi, Adriano
Zenobi, Renato
Journal or Series Title Journal of mass spectrometry
Volume Number 44
Issue Number 6
Start Page 965
End Page 977
ISSN 1076-5174
1076-5164
1096-9888
Publisher Wiley
Publication Place Chichester
Publication Date 2009
Keyword(s) amyloid prion protein
fibril formation
recombinant amyloidogenic prion
hydrogen/deuterium exchange
ion trap mass spectrometry
Abstract Understanding the structural basis that distinguishes the amyloid form of the prion protein from its monomeric homologue is of crucial importance to elucidate the mechanism of the lethal diseases related to this protein. Recently, an in vitro conversion system was established which reproduces the transition of recombinant prion protein PrP(23-230) from its native -helical rich form into an aggregated amyloid -sheet rich form with physicochemical properties reminiscent to those of the disease-related isoform of the prion protein, PrPSc. To study the tertiary and quaternary structural organization within recombinant amyloid fibrils from mouse, mPrP(23-231)f; bovine, bPrP(23-230)f; and elk, ePrP(23-230)f; we utilized hydrogen/deuterium (H/D) exchange analyzed by matrix-assisted laser desorption/ionization (MALDI) and nano-electrospray (nano-ESI) mass spectrometry. No significant differences were found by measuring the deuterium exchange kinetics of the aggregated fibrillar forms for mPrP(23-231)f, bPrP(23-230)f and ePrP(23-230)f, indicating a similar overall structural organization of the fibrils from all three species. Next, we characterized the solvent accessibility for the soluble and fibrillar forms of the mouse prion protein by hydrogen exchange, pepsin proteolysis and nano-ESI ion trap mass spectrometry analysis. In its amyloid form, two highly protected regions of mPrP(23-231) comprising residues [24-98] and [182-212] were identified. The residues between the two highly protected stretches were found to be more solvent exposed, but less than in the soluble protein, and might therefore rather form part of a fibrillar interface.
DOI 10.1002/jms.1572
Additional Notes Received 3 July 2008, Accepted 2 February 2009, Published online 12 March 2009
Document Type Article
Publication Status Published
Language English
Assigned Organisational Unit(s) 03430
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NEBIS System Number 001410098
Source Database ID PP-51485
WOS-000267445200010
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@article{Nzbl2009,
  author = "Nazabal, Alexis and Hornemann, Simone and Aguzzi, Adriano and Zenobi, Renato",
  title = "{H}ydrogen/deuterium exchange mass spectrometry identifies two highly protected regions in recombinant full-length prion protein amyloid fibrils",
  journal = "Journal of mass spectrometry",
  year = 2009,
  volume = "44",
  number = "6",
  pages = "965--977",
}


E-Citations record created: Wed, 23 Jun 2010, 20:48:46 CET