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The Causes and Consequences of Nonenzymatic Protein Acylation.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

James, Andrew M 
Smith, Cassandra L 
Smith, Anthony C 
Robinson, Alan J 
Hoogewijs, Kurt 

Abstract

Thousands of protein acyl modification sites have now been identified in vivo. However, at most sites the acylation stoichiometry is low, making functional enzyme-driven regulation in the majority of cases unlikely. As unmediated acylation can occur on the surface of proteins when acyl-CoA thioesters react with nucleophilic cysteine and lysine residues, slower nonenzymatic processes likely underlie most protein acylation. Here, we review how nonenzymatic acylation of nucleophilic lysine and cysteine residues occurs; the factors that enhance acylation at particular sites; and the strategies that have evolved to limit protein acylation. We conclude that protein acylation is an unavoidable consequence of the central role of reactive thioesters in metabolism. Finally, we propose a hypothesis for why low-stoichiometry protein acylation is selected against by evolution and how it might contribute to degenerative processes such as aging.

Description

Keywords

Acyl Coenzyme A, Acylation, Animals, Cysteine, Humans, Lysine, Protein Processing, Post-Translational, Proteins

Journal Title

Trends Biochem Sci

Conference Name

Journal ISSN

0968-0004
1362-4326

Volume Title

43

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_UU_00015/3)
Wellcome Trust (110159/Z/15/Z)
Medical Research Council (MC_U105663142)
Medical Research Council (MC_U105674181)