Lysine Phoshoglycerylation Is Widespread in Bacteria and Overlaps with Acylation

TL;DR

This study shows that lysine phosphoglycerylation is common in bacteria and often overlaps with other acylations, suggesting a possible role in metabolic regulation.

Contribution

The first proteomic analysis of lysine phosphoglycerylation in bacteria, revealing its prevalence and overlap with acylation.

Findings

370 phosphoglycerylation sites were identified in 123 proteins of Streptococcus pyogenes.

Phosphoglycerylation was more abundant in fructose-based media compared to glucose-based media.

Phosphoglycerylation overlaps with acetylation and other acylations on the same lysine residues in bacteria.

Abstract

Phosphoglycerylation is a non-enzymatic protein modification in which a phosphoglyceryl moiety is covalently bound to the ε-amino group of lysine. It is enriched in glycolytic enzymes from humans and mice and is thought to provide a feedback mechanism for regulating glycolytic flux. We report the first proteomic analysis of this post-translational modification in bacteria by profiling phosphoglyceryl-lysine during the growth of Streptococcus pyogenes in different culture media. The identity of phosphoglyceryl-lysine was confirmed by a previously unknown diagnostic cyclic immonium ion generated during MS/MS. We identified 370 lysine phosphoglycerylation sites in 123 proteins of S. pyogenes. Growth in a defined medium on 1% fructose caused a significant accumulation of phosphoglycerylation compared to growth in a rich medium containing 0.2% glucose. Re-analysis of phosphoproteomes from 14 bacterial species revealed that phosphoglycerylation is generally widespread in bacteria. Many phosphoglycerylation sites were conserved in several bacteria, including S. pyogenes. There was considerable overlap between phosphoglycerylation, acetylation, succinylation, and other acylations on the same lysine residues. Despite some exceptions, most lysine phosphoglycerylations in S. pyogenes occurred with low stoichiometry. Such modifications may be meaningless, but it is also conceivable that phosphoglycerylation, acetylation, and other acylations jointly contribute to the overall regulation of metabolism.

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