L17A/F19A Substitutions Augment the α-Helicity of β-Amyloid Peptide Discordant Segment
Autor: | Chu-Ting Liang, Yi-Cheng Chen, Chih Ching Wang, Hsien-Bin Huang, Ta Hsien Lin, Ming-Shi Shiao, Chi-Fon Chang, Yi Ru Chen |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Circular dichroism Magnetic Resonance Spectroscopy lcsh:Medicine Peptide medicine.disease_cause Spectrum analysis techniques 01 natural sciences Biochemistry Protein Structure Secondary Pathogenesis Isotopes Medicine and Health Sciences Amino Acids lcsh:Science Alanine chemistry.chemical_classification Mutation Multidisciplinary Chemistry Organic Compounds Circular Dichroism Neurodegenerative Diseases Absorption Spectroscopy Nuclear magnetic resonance spectroscopy Helicity Lipids Circular Dichroism Spectroscopy Neurology Physical Sciences Research Article Substitution Mutation 010402 general chemistry 03 medical and health sciences NMR spectroscopy Alzheimer Disease Lipid Structure Mental Health and Psychiatry medicine Genetics Humans Amyloid beta-Peptides Point mutation lcsh:R Organic Chemistry Chemical Compounds Biology and Life Sciences Proteins 0104 chemical sciences Research and analysis methods 030104 developmental biology Aliphatic Amino Acids Biophysics lcsh:Q Dementia Peptides |
Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 4, p e0154327 (2016) |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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