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The Arctic mutation alters helix length and type in the 11-28 beta-amyloid peptide monomer-CD, NMR and MD studies in an SDS micelle.
- Source :
-
Journal of structural biology [J Struct Biol] 2008 Nov; Vol. 164 (2), pp. 199-209. Date of Electronic Publication: 2008 Aug 14. - Publication Year :
- 2008
-
Abstract
- The beta-amyloid (Abeta) is the major peptide constituent of neuritic plaques in Alzheimer's disease, and its aggregation is believed to play a central role in the pathogenesis of the disease. Naturally occurring mutations resulting in changes in the Abeta sequence (pos. 21-23) are associated with familial Alzheimer's-like diseases with extensive cerebrovascular pathology. It has been demonstrated that such mutations alter the aggregation ability of Abeta and its neurotoxicity. Among the five mutations at positions 21-23 there is one with distinct clinical characteristics and a potentially distinct pathogenic mechanism-the Arctic (E22G) mutation. We have examined the structures of fragment 11-28 of the native peptide and its E22G variant. This fragment was chosen because it has been shown to be a good model for conformational and aggregation studies as it contains the hydrophobic core responsible for aggregation and the residues critical to alpha-secretase cleavage of APP. The detailed structure of the two peptides was determined using CD, 2D NMR and molecular dynamics techniques under water-SDS micelle conditions. Our studies indicated the existence of partially alpha- and 3(10)-helical conformations in the native and mutated peptide, respectively.
- Subjects :
- Circular Dichroism
Humans
Magnetic Resonance Spectroscopy
Molecular Dynamics Simulation
Peptide Fragments chemistry
Peptide Fragments genetics
Protein Structure, Secondary genetics
Amyloid beta-Peptides chemistry
Amyloid beta-Peptides genetics
Micelles
Mutation, Missense
Sodium Dodecyl Sulfate
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8657
- Volume :
- 164
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of structural biology
- Publication Type :
- Academic Journal
- Accession number :
- 18765285
- Full Text :
- https://doi.org/10.1016/j.jsb.2008.07.010