Influence of the familial Alzheimer's disease-associated T43I mutation on the transmembrane structure and γ-secretase processing of the C99 peptide.
Alzheimer disease
Aβ42/Aβ40 ratio
Fourier transform IR (FTIR)
amyloid precursor protein (APP)
amyloid-beta (Aβ)
fluorescence
membrane interaction
neurodegeneration
nuclear magnetic resonance (NMR)
secretase
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
12 04 2019
12 04 2019
Historique:
received:
07
10
2018
revised:
09
02
2019
pubmed:
14
2
2019
medline:
15
10
2019
entrez:
14
2
2019
Statut:
ppublish
Résumé
Extracellular deposition of β-amyloid (Aβ) peptides in the brain is a hallmark of Alzheimer's disease (AD). Upon β-secretase-mediated cleavage of the β C-terminal fragment (β-CTF) from the Aβ precursor protein, the γ-secretase complex produces the Aβ peptides associated with AD. The familial T43I mutation within the transmembrane domain of the β-CTF (also referred to as C99) increases the ratio between the Aβ42 and Aβ40 peptides largely due to a decrease in Aβ40 formation. Aβ42 is the principal component of amyloid deposits within the brain parenchyma, and an increase in the Aβ42/Aβ40 ratio is correlated with early-onset AD. Using NMR and FTIR spectroscopy, here we addressed how the T43I substitution influences the structure of C55, the minimal sequence containing the entire extracellular and transmembrane (TM) domains of C99 needed for γ-secretase processing.
Identifiants
pubmed: 30755484
pii: S0021-9258(20)36658-8
doi: 10.1074/jbc.RA118.006061
pmc: PMC6463720
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Peptide Fragments
0
Peptides
0
amyloid beta-protein (1-40)
0
amyloid beta-protein (1-42)
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5854-5866Subventions
Organisme : NIA NIH HHS
ID : R01 AG027317
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG027317
Pays : United States
Informations de copyright
© 2019 Tang et al.
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