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Spontaneous protein-protein crosslinking at glutamine and glutamic acid residues in long-lived proteins.

ABSTRACT: 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.

SUBMITTER: Friedrich MG

PROVIDER: S-EPMC9188286 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Spontaneous protein-protein crosslinking at glutamine and glutamic acid residues in long-lived proteins.

Friedrich Michael G MG Wang Zhen Z Schey Kevin L KL Truscott Roger J W RJW

The Biochemical journal 20210101 2

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 ...[more]

PMID: 33345277

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Dataset Information

Spontaneous protein-protein crosslinking at glutamine and glutamic acid residues in long-lived proteins.

Publications

Spontaneous protein-protein crosslinking at glutamine and glutamic acid residues in long-lived proteins.

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