Beta-Secretase 1 Recruits Amyloid-Beta Precursor Protein to ROCK2 Kinase, Resulting in Erroneous Phosphorylation and Beta-Amyloid Plaque Formation.
allosteric binding site
amyloid precursor protein (APP)
beta-secretase (BACE1)
phosphorylation
rho-kinase (ROCK)
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
21 Jun 2023
21 Jun 2023
Historique:
received:
31
05
2023
revised:
13
06
2023
accepted:
16
06
2023
medline:
17
7
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
epublish
Résumé
The amyloidogenic processing of APP depends on two events: its phosphorylation by ROCK2 (at Thr654) and the phosphorylation of the APP-cleaving enzyme BACE1 (at Ser498). However, the mechanisms and structural details of APP-ROCK2 and BACE1-ROCK2 binding are unknown. Using direct physical methods in combination with an in silico approach, we found that BACE1 binds into the substrate-binding groove of ROCK2 with a low affinity (K
Identifiants
pubmed: 37445593
pii: ijms241310416
doi: 10.3390/ijms241310416
pmc: PMC10341550
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Aspartic Acid Endopeptidases
EC 3.4.23.-
Amyloid beta-Protein Precursor
0
ROCK2 protein, human
EC 2.7.11.1
rho-Associated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Hungarian Scientific Research Fund
ID : K134711
Organisme : Hungarian Scientific Research Fund
ID : K128262
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