Identification of lysine succinylation as a new post-translational modification

By Zhihong Zhang, M. Tan, Zhongyu Xie, Lunzhi Dai, Yue Chen, Tingming Zhao. Nature Chemical Biology, 2010

914 citations recorded by the source corpus.

Of the 20 ribosomally coded amino acid residues, lysine is the most frequently post-translationally modified, which has important functional and regulatory consequences. Here we report the identification and verification of a previously unreported form of protein post-translational modification (PTM): lysine succinylation. The succinyllysine residue was initially identified by mass spectrometry and protein sequence alignment. The identified succinyllysine peptides derived from in vivo proteins were verified by western blot analysis, in vivo labeling with isotopic succinate, MS/MS and HPLC coelution of their synthetic counterparts. We further show that lysine succinylation is evolutionarily conserved and that this PTM responds to different physiological conditions. Our study also implies that succinyl-CoA might be a cofactor for lysine succinylation. Given the apparent high abundance of lysine succinylation and the significant structural changes induced by this PTM, it is expected that lysine succinylation has important cellular functions.

Subfields: Geriatrics and Gerontology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/4609ec9f22917662418e4399b9cd527f2b6ee62a

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Citations in the corpus

Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “However, it was not until 2011 that succinylation was identified as a natural PTM of lysine residues in bacteria by affinity purification with antisuccinyl lysine antibody (Zhang et al., 2011; Alleyn et al., 2018; Sreedhar et al., 2020).”
SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways (2013, background): “Mutations in the IDH2 gene, a mammalian IDH homolog, causes D-2 hydroxyglutaric aciduria type 2 (D2HGA2) (Kranendijk et al., 2010), whereas its downregulation leads to epigenetic dysfunction via the loss of 5-hydroxymethyl-cytosine in melanoma (Lian et al., 2012).”
Lysine Glutarylation Is a Protein Post-Translational Modification Regulated by SIRT5 (2014, background): “Succinate and malonate can be used by cells to generate lysine succinylation and malonylation, respectively, presumably by generating succinyl-CoA and malonyl-CoA intermediary metabolites (Peng et al., 2011; Zhang et al., 2011).”
pSuc-Lys: Predict lysine succinylation sites in proteins with PseAAC and ensemble random forest approach. (2016, background): “Further studies showed that the lysine succinylation responses to different physiological conditions and is evolutionarily conserved [3].”
The First Identification of Lysine Malonylation Substrates and Its Regulatory Enzyme* (2011, methodology): “Recently, we identified a new type of PTM at lysine residues, lysine succinylation (7).”
SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks (2013, neutral): “Lysine succinylation is found from yeast to mammal (Zhang et al., 2011).”
Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. (2013, methodology): “The enrichment of succinylated peptides with succinyllysine antibody, and the verification of lysine succinylation by orthogonal methods, were validated in a previous study (Zhang et al., 2011).”
Unraveling the Complex Interplay Between T Cell Metabolism and Function (2018, background): “In addition to the well-established phosphorylation (ATP) and acetylation of proteins (acetate), other TCA intermediates such as malate and succinate can be used to modify proteins through malonylation (43) and succinylation (44), respectively.”