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
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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