期刊
JOURNAL OF PROTEOME RESEARCH
卷 19, 期 10, 页码 4163-4178出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.0c00685
关键词
post-translational modifications; methylation; acetylation; succinylation; data-independent acquisition mass spectrometry (DIA-MS); peptidoforms; spectral library; nonalcoholic steatohepatitis
资金
- US National Institutes of Health (NIH) [R01DK107288]
- NIH [GM110174, AI118891]
- Agencia Estatal de Investigacion Grant MINECO [SAF 2017-88041-R]
- Agencia Estatal de Investigacion Grant ISCiii [PIE14/00031 CIBERehd-ISCiii]
- Agencia Estatal de Investigacion Grant Severo Ochoa Excellence Accreditation [SEV-2016-0644]
Proteoforms containing post-translational modifications (PTMs) represent a degree of functional diversity only harnessed through analytically precise simultaneous quantification of multiple PTMs. Here we present a method to accurately differentiate an unmodified peptide from its PTM-containing counterpart through data-independent acquisition-mass spectrometry, leveraging small precursor mass windows to physically separate modified peptidoforms from each other during MS2 acquisition. We utilize a lysine and arginine PTM-enriched peptide assay library and site localization algorithm to simultaneously localize and quantify seven PTMs including mono-, di-, and trimethylation, acetylation, and succinylation in addition to total protein quantification in a single MS run without the need to enrich experimental samples. To evaluate biological relevance, this method was applied to liver lysate from differentially methylated nonalcoholic steatohepatitis (NASH) mouse models. We report that altered methylation and acetylation together with total protein changes drive the novel hypothesis of a regulatory function of PTMs in protein synthesis and mRNA stability in NASH.
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