uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Oxidation of Methionine-35 Attenuates Formation of Amyloid β-Peptide 1-40 Oligomers
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Ion Physics.
2002 (English)In: Journal of chemical biology, ISSN 1864-6158, E-ISSN 1864-6166, Vol. 277, 19506-19510 p.Article in journal (Refereed) Published
Abstract [en]

Amyloid plaques formed by aggregation of the amyloid β-peptide (Aβ) are an intrinsic component of Alzheimer disease pathogenesis. It has been suggested that oxidation of methionine 35 in Aβ has implications for Alzheimer disease, and it has been shown that oxidation of Met-35 significantly inhibits aggregation in vitro. In this study, the aggregational properties of Aβ-(1–40) before and after Met-35 oxidation were investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The results show that Aβ-(1–40)Met-35(O) trimer and tetramer formation is significantly attenuated as compared with Aβ-(1–40). This suggests that oxidation of Met-35 inhibits a conformational switch in Aβ-(1–40) necessary for trimer but not dimer formation. Random incorporation of Aβ-(1–40) and Aβ-(1–40)Met-35(O) in homo- and heterooligomers could also be observed. This is the first report of an early rate-limiting step in Aβ-(1–40) aggregation. Slowing of the fibrillization process at this early step is likely to support prolonged solubility and clearance of Aβ from brain and may reduce disease progression.

Place, publisher, year, edition, pages
2002. Vol. 277, 19506-19510 p.
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-89822DOI: 10.1074/jbc.M112218200OAI: oai:DiVA.org:uu-89822DiVA: diva2:161607
Available from: 2002-04-23 Created: 2002-04-23 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Identification and Characterization of Peptides and Proteins using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
Open this publication in new window or tab >>Identification and Characterization of Peptides and Proteins using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mass spectrometry has in recent years been established as the standard method for protein identification and characterization in proteomics with excellent intrinsic sensitivity and specificity. Fourier transform ion cyclotron resonance is the mass spectrometric technique that provides the highest resolving power and mass accuracy, increasing the amount of information that can be obtained from complex samples. This thesis concerns how useful information on proteins of interest can be extracted from mass spectrometric data on different levels of protein structure and how to obtain this data experimentally. It was shown that it is possible to analyze complex mixtures of protein tryptic digests by direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and identify abundant proteins by peptide mass fingerprinting. Coupling on-line methods such as liquid chromatography and capillary electrophoresis increased the number of proteins that could be identified in human body fluids. Protein identification was also improved by novel statistical methods utilizing prediction of chromatographic behavior and the non-randomness of enzymatic digestion. To identify proteins by short sequence tags, electron capture dissociation was implemented, improved and finally coupled on-line to liquid chromatography for the first time. The combined techniques can be used to sequence large proteins de novo or to localize and characterize any labile post-translational modification. New computer algorithms for the automated analysis of isotope exchange mass spectra were developed to facilitate the study of protein structural dynamics. The non-covalent interaction between HIV-inhibitory peptides and the oligomerization of amyloid β-peptides were investigated, reporting several new findings with possible relevance for development of anti-HIV drug therapies and understanding of fundamental mechanisms in Alzheimer’s disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 76 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 706
Keyword
Materials science, Peptide, protein, peptide mass fingerprinting, identification, sequencing, protein structure, non-covalent interaction, modification, electrospray ionization, liquid chromatography, capillary electrophoresis, electron capture dissociation, Fourier transform ion cyclotron resonance mass spectrometry, cerebrospinal fluid, amyloid β-peptide, Alzheimer’s disease., Materialvetenskap
National Category
Materials Engineering
Research subject
Molecular Biotechnology
Identifiers
urn:nbn:se:uu:diva-1999 (URN)91-554-5296-5 (ISBN)
Public defence
2002-05-17, Siegbahnsalen, Uppsala, 10:00 (English)
Opponent
Available from: 2002-04-23 Created: 2002-04-23 Last updated: 2010-01-14Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Bergquist, Jonas

Search in DiVA

By author/editor
Bergquist, Jonas
By organisation
Ion PhysicsAnalytical Chemistry
In the same journal
Journal of chemical biology
Analytical Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 886 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf