Spontaneous protein-protein crosslinking at glutamine and glutamic acid residues in long-lived proteins.
Alzheimer's disease
age
human lens
long-lived proteins
protein crosslinks
Journal
The Biochemical journal
ISSN: 1470-8728
Titre abrégé: Biochem J
Pays: England
ID NLM: 2984726R
Informations de publication
Date de publication:
29 01 2021
29 01 2021
Historique:
received:
18
10
2020
revised:
15
12
2020
accepted:
18
12
2020
pubmed:
22
12
2020
medline:
30
4
2021
entrez:
21
12
2020
Statut:
ppublish
Résumé
Long-lived proteins (LLPs) are susceptible to the accumulation of both enzymatic and spontaneous post-translational modifications (PTMs). A prominent PTM observed in LLPs is covalent protein-protein crosslinking. In this study, we examined aged human lenses and found several proteins to be crosslinked at Glu and Gln residues. This new covalent bond involves the amino group of Lys or an α-amino group. A number of these crosslinks were found in intermediate filament proteins. Such crosslinks could be reproduced experimentally by incubation of Glu- or Gln-containing peptides and their formation was consistent with an amino group attacking a glutarimide intermediate. These findings show that both Gln and Glu residues can act as sites for spontaneous covalent crosslinking in LLPs and they provide a mechanistic explanation for an otherwise puzzling observation, that a major fraction of Aβ in the human brain is crosslinked via Glu 22 and the N-terminal amino group.
Identifiants
pubmed: 33345277
pii: 227396
doi: 10.1042/BCJ20200798
pmc: PMC9188286
mid: NIHMS1813048
doi:
Substances chimiques
Eye Proteins
0
Piperidones
0
Glutamine
0RH81L854J
Glutamic Acid
3KX376GY7L
Lysine
K3Z4F929H6
glutarimide
MV728O9612
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
327-339Subventions
Organisme : NEI NIH HHS
ID : P30 EY008126
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024258
Pays : United States
Informations de copyright
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
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