L17A/F19A Substitutions Augment the α-Helicity of β-Amyloid Peptide Discordant Segment.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27104649.
- Also identified by DOI 10.1371/journal.pone.0154327 and PMC identifier 4841593.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
β-amyloid peptide (Aβ) aggregation has been thought to be associated with the pathogenesis of Alzheimer's disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aβ40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aβ40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/β-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aβ40. These results provide a structural basis to link the α-helicity of the α/β-discordant segment with the conformational conversion propensity of Aβ.
Medical subject headings
- Alzheimer Disease
- Amyloid beta-Peptides