Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • 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
NMR studies of the amyloid beta-peptide
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The Amyloid beta peptide (Ab) is related to Alzheimer’s disease and is suggested to be the molecular pathogenic species of the disease, probably through the neurotoxic effect of Ab oligomers. Here the results from biophysical studies of Ab and fragments thereof, are presented. Pulsed field gradient NMR diffusion experiments show that Ab exists mainly as an unfolded monomer. In addition, the hydrodynamic radius of Ab suggests that Ab has residual secondary structure propensities. CD experiments reveal that Ab has a high propensity to adopt a polyproline type II (PII) helix at low temperature. NMR diffusion measurements as well as the 3JHNH values show that increasing the temperature from 4 C induces a structure transition from PII propensity to a beta strand propensity around 15 C and to a random coil conformation at higher temperature. The small hydrodynamic radius at low temperature may be explained by the presence of a population of a hairpin conformation as was suggested by MD simulations. 15N relaxation and secondary chemical shifts suggest that Ab consists of 6 structural regions, two regions with high PII propensity are separated by a highly mobile region located in the N-terminal part of the peptide. In the C-terminal part two regions with a propensity to adopt b-strand are located, separated by a mobile region. The structural propensities of soluble monomeric Ab agree well with the structure of the peptide in fibril aggregates as well as in SDS micelles. Ab binds zinc specifically and with high affinity. This interaction was studied using heteronuclear correlation experiments. The metal ligands were determined to be three histidines, 6,13 and 14 and the N-terminus. The Ab peptide also binds b-cyclodextrin and the combined use of NMR diffusion experiments and induced chemical shifts show that Ab has at least two binding sites for b-cyclodextrin, and the dissociation constants of these binding sites were determined.

Place, publisher, year, edition, pages
Stockholm: Institutionen för biokemi och biofysik , 2007. , 86 p.
Keyword [en]
NMR, amyloid beta peptide, structure, metal interaction, diffusion
National Category
Biophysics
Identifiers
URN: urn:nbn:se:su:diva-1410ISBN: 91-7155-349-5 (print)OAI: oai:DiVA.org:su-1410DiVA: diva2:190048
Public defence
2007-01-26, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
Opponent
Supervisors
Available from: 2007-01-02 Created: 2007-01-02Bibliographically approved
List of papers
1. Translational diffusion measured by PFG-NMR on full length and fragments of the Alzheimer Aβ(1-40) peptide. Determination of hydrodynamic radii of random coil peptides of varying length
Open this publication in new window or tab >>Translational diffusion measured by PFG-NMR on full length and fragments of the Alzheimer Aβ(1-40) peptide. Determination of hydrodynamic radii of random coil peptides of varying length
2002 In: Magnetic Resonance in Chemistry, ISSN 0749-1581, Vol. 40, no 13, S89-S97 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23074 (URN)
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02Bibliographically approved
2. A left-handed 31 helical conformation in the Alzheimer Aβ(12-28) peptide
Open this publication in new window or tab >>A left-handed 31 helical conformation in the Alzheimer Aβ(12-28) peptide
Show others...
2003 In: FEBS Letters, ISSN 0014-5793, Vol. 555, no 2, 371-374 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23075 (URN)
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02Bibliographically approved
3. Two-Site Binding of β-Cyclodextrin to the Alzheimer Aβ(1-40) Peptide Measured with Combined PFG-NMR Diffusion and Induced Chemical Shifts
Open this publication in new window or tab >>Two-Site Binding of β-Cyclodextrin to the Alzheimer Aβ(1-40) Peptide Measured with Combined PFG-NMR Diffusion and Induced Chemical Shifts
2004 In: Biochemistry, ISSN 0006-2960, Vol. 43, 6261-6269 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23076 (URN)
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02Bibliographically approved
4. The Alzheimer β-peptide shows temperature-dependent transitions between left-handed 31-helix, β-strand and random coil secondary structures
Open this publication in new window or tab >>The Alzheimer β-peptide shows temperature-dependent transitions between left-handed 31-helix, β-strand and random coil secondary structures
2005 In: FEBS Journal, ISSN 1742-464X, Vol. 272, no 15, 3938-3949 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23077 (URN)
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02Bibliographically approved
5. 15N-relaxation study of the Alzheimer β-peptide: structural propensities and persistence length
Open this publication in new window or tab >>15N-relaxation study of the Alzheimer β-peptide: structural propensities and persistence length
2006 In: Magnetic Resonance in Chemistry, ISSN 0749-1581, Vol. 44, no S1, S114-S121 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23078 (URN)
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02Bibliographically approved
6. High-resolution NMR studies of the sinc-binding site of the Alzheimer’s Aβ-peptide
Open this publication in new window or tab >>High-resolution NMR studies of the sinc-binding site of the Alzheimer’s Aβ-peptide
2007 (English)In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 274, no 1, 46-59 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-23079 (URN)10.1111/j.1742-4658.2006.05563.x (DOI)000242782600004 ()
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02 Last updated: 2017-12-13Bibliographically approved
7. Structure and positioning of the Alzheimer Aβ(1-40) peptide in SDS micelles using NMR and paramagnetic probes
Open this publication in new window or tab >>Structure and positioning of the Alzheimer Aβ(1-40) peptide in SDS micelles using NMR and paramagnetic probes
Show others...
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-23080 (URN)
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02 Last updated: 2010-01-13Bibliographically approved
8. Structure of the Amyloid β-peptide Fragment 1-9, A combined molecular dynamics and NMR study
Open this publication in new window or tab >>Structure of the Amyloid β-peptide Fragment 1-9, A combined molecular dynamics and NMR study
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-23081 (URN)
Note
Part of urn:nbn:se:su:diva-1410Available from: 2007-01-02 Created: 2007-01-02 Last updated: 2010-01-13Bibliographically approved

Open Access in DiVA

fulltext(6296 kB)2117 downloads
File information
File name FULLTEXT01.pdfFile size 6296 kBChecksum SHA-1
d4dd9724eceabd9d6bf51a24cdb2417bd10b5fc539568a99393aa1c3ffdbfd600691af77
Type fulltextMimetype application/pdf

By organisation
Department of Biochemistry and Biophysics
Biophysics

Search outside of DiVA

GoogleGoogle Scholar
Total: 2117 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 975 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • 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