Chemoproteomic identification of CO 2 -dependent lysine carboxylation in proteins.

Autor: King DT; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada., Zhu S; Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada., Hardie DB; University of Victoria-Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada., Serrano-Negrón JE; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada., Madden Z; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada., Kolappan S; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada., Vocadlo DJ; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada. dvocadlo@sfu.ca.; Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada. dvocadlo@sfu.ca.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2022 Jul; Vol. 18 (7), pp. 782-791. Date of Electronic Publication: 2022 Jun 16.
DOI: 10.1038/s41589-022-01043-1
Abstrakt: Carbon dioxide is an omnipresent gas that drives adaptive responses within organisms from all domains of life. The molecular mechanisms by which proteins serve as sensors of CO 2 are, accordingly, of great interest. Because CO 2 is electrophilic, one way it can modulate protein biochemistry is by carboxylation of the amine group of lysine residues. However, the resulting CO 2 -carboxylated lysines spontaneously decompose, giving off CO 2 , which makes studying this modification difficult. Here we describe a method to stably mimic CO 2 -carboxylated lysine residues in proteins. We leverage this method to develop a quantitative approach to identify CO 2 -carboxylated lysines of proteins and explore the lysine 'carboxylome' of the CO 2 -responsive cyanobacterium Synechocystis sp. We uncover one CO 2 -carboxylated lysine within the effector binding pocket of the metabolic signaling protein PII. CO 2 -carboxylatation of this lysine markedly lowers the affinity of PII for its regulatory effector ligand ATP, illuminating a negative molecular control mechanism mediated by CO 2 .
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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