New insights into the mechanisms of age-related protein-protein crosslinking in the human lens.
Dehydroalanine
Long-lived proteins
Mass spectrometry
Protein crosslinking
Succinimide
Journal
Experimental eye research
ISSN: 1096-0007
Titre abrégé: Exp Eye Res
Pays: England
ID NLM: 0370707
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
18
03
2021
revised:
11
06
2021
accepted:
14
06
2021
pubmed:
21
6
2021
medline:
1
12
2021
entrez:
20
6
2021
Statut:
ppublish
Résumé
Although protein crosslinking is often linked with aging as well as some age-related diseases, very few molecular details are available on the nature of the amino acids involved, or mechanisms that are responsible for crosslinking. Recent research has shown that several amino acids are able to generate reactive intermediates that ultimately lead to covalent crosslinking through multiple non-enzymatic mechanisms. This information has been derived from proteomic investigations on aged human lenses and the mechanisms of crosslinking, in each case, have been elucidated using model peptides. Residues involved in spontaneous protein-protein crosslinking include aspartic acid, asparagine, cysteine, lysine, phosphoserine, phosphothreonine, glutamic acid and glutamine. It has become clear, therefore, that several amino acids can act as potential sites for crosslinking in the long-lived proteins that are present in aged individuals. Moreover, the lens has been an invaluable model tissue and source of crosslinked proteins from which to determine crosslinking mechanisms that may lead to crosslinking in other human tissues.
Identifiants
pubmed: 34147508
pii: S0014-4835(21)00245-1
doi: 10.1016/j.exer.2021.108679
pmc: PMC8595514
mid: NIHMS1719401
pii:
doi:
Substances chimiques
Crystallins
0
Eye Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
108679Subventions
Organisme : NEI NIH HHS
ID : P30 EY008126
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY013462
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY013570
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY024258
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
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