Cysteine S-acetylation is a post-translational modification involved in metabolic regulation

Keenan, E. Keith; Bareja, Akshay; Lam, Yannie; Grimsrud, Paul; Hirschey, Matthew

doi:10.5281/zenodo.11580331

Published June 11, 2024 | Version v1

Dataset Open

Cysteine S-acetylation is a post-translational modification involved in metabolic regulation

1. Duke University
2. Duke University School of Medicine

Cysteine is a reactive amino acid central to the catalytic activities of many enzymes. It is also a common target of post-translational modifications (PTMs), such as palmitoylation. This long-chain acyl PTM can modify cysteine residues and induce changes in protein subcellular localization. We hypothesized that cysteine could also be modified by short-chain acyl groups, such as cysteine S-acetylation. To test this, we developed sample preparation and non-targeted mass spectrometry protocols to analyze the mouse liver proteome for cysteine acetylation. Our findings revealed hundreds of sites of cysteine acetylation across multiple tissue types, revealing a previously uncharacterized cysteine acetylome. Cysteine acetylation shows a marked cytoplasmic subcellular localization signature, with tissue-specific acetylome patterns and specific changes upon metabolic stress. This study uncovers a novel aspect of cysteine biochemistry, highlighting short-chain modifications alongside known long-chain acyl PTMs. These findings enrich our understanding of the landscape of acyl modifications and suggest new research directions in enzyme activity regulation and cellular signaling in metabolism.

Notes

These are 3 Supplemental Tables, and 48 raw Supplemental Datasets accompanying a manuscript of the same title.

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Files (563.8 MB)

Name	Size	Download all
Supplemental Dataset 1. All Acetyl-Cys Peptide groups _ all columns _ 20190909_TCEPvDTTround2_20191011.xlsx md5:8c9589fc1bb3d360b5ee7a92fcc67a5d	221.2 kB	Download
Supplemental Dataset 10. All Acetyl-Cys Peptide groups _ all columns _ 20230330EKK20230327_LiverCellFrac_PD20230403.xlsx md5:b60b47e238b676779220011710001ef9	309.2 kB	Download
Supplemental Dataset 11. All Peptide groups _ all columns _ 20230330EKK20230327_LiverCellFrac_PD20230403.xlsx md5:32222919cbd91c2155a35975dd17e6c2	27.3 MB	Download
Supplemental Dataset 12. All Proteins _ all columns _ 20230330EKK20230327_LiverCellFrac_PD20230403.xlsx md5:9e405e1a4a511da42134ab3de68b9876	20.0 MB	Download
Supplemental Dataset 13. All Acetyl-Cys Peptide groups _ all columns _ 20240104EKK20231218_AcetylCysTissueScreen_PD20240110-(13).xlsx md5:ef25dd92b3d72eac6080b2dc19946269	644.8 kB	Download
Supplemental Dataset 14. All Peptide groups _ all columns _ 20240104EKK20231218_AcetylCysTissueScreen_PD20240110-(13).xlsx md5:04f6947738ef73126f082ba49b2b4648	290.4 MB	Download
Supplemental Dataset 15. All Proteins _ all columns _ 20240104EKK20231218_AcetylCysTissueScreen_PD20240110-(13).xlsx md5:3f28dc0ae1381afb2539bb6de41c6631	30.0 MB	Download
Supplemental Dataset 16. BAT_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_BAT.xlsx md5:f4bebab6cf91c56af9de9ba5c847e2f1	53.9 kB	Download
Supplemental Dataset 17. BAT_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_BAT.xlsx md5:49719f19753be8842a8ca72c72724f69	4.2 MB	Download
Supplemental Dataset 18. BAT_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_BAT.xlsx md5:87d739297982fed4c74a288d229358fe	5.1 MB	Download
Supplemental Dataset 19. Brain_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Brain.xlsx md5:0da914f0f004b3db6e169e555ea6de18	62.7 kB	Download
Supplemental Dataset 2. All Peptide groups _ all columns _ 20190909_TCEPvDTTround2_20191011.xlsx md5:30b25fa3bb78730513d2f2ba01c90905	13.2 MB	Download
Supplemental Dataset 20. Brain_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Brain.xlsx md5:1757d3d033580d7df83eeb9fa24314ef	5.8 MB	Download
Supplemental Dataset 21. Brain_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Brain.xlsx md5:0049c6fd025ac68336c55e85b3166fd6	7.6 MB	Download
Supplemental Dataset 22. Heart_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Heart.xlsx md5:ea2edc9f64e8089617b33e58f9caf47f	45.7 kB	Download
Supplemental Dataset 23. Heart_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Heart.xlsx md5:cbb622a10f8f371bf9f66315eb131688	3.2 MB	Download
Supplemental Dataset 24. Heart_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Heart.xlsx md5:1433f0a5f485291354206d7e5f4a8173	3.9 MB	Download
Supplemental Dataset 25. Kidney_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Kidney.xlsx md5:1008929ab8751f9b55a7dfdf2900ab1d	65.2 kB	Download
Supplemental Dataset 26. Kidney_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Kidney.xlsx md5:7b110bf2785f55e5a0dc63b5a893f93f	4.6 MB	Download
Supplemental Dataset 27. Kidney_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Kidney.xlsx md5:d7ad190c04cbccee258b416b49f8f7cc	6.1 MB	Download
Supplemental Dataset 28. Liver_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Liver.xlsx md5:4f9321555acf6da16cc302e57f9d97f8	65.7 kB	Download
Supplemental Dataset 29. Liver_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Liver.xlsx md5:fcb4e134b729823cb76ef8cc411573f9	4.5 MB	Download
Supplemental Dataset 3. All Proteins _ all columns _ 20190909_TCEPvDTTround2_20191011.xlsx md5:bbb39ae2248fbb337d5d0f45deead3f9	12.0 MB	Download
Supplemental Dataset 30. Liver_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Liver.xlsx md5:09b31a0080dca712be92385e31ac4eb9	5.5 MB	Download
Supplemental Dataset 31. Lung_ All Acetyl_Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Lung.xlsx md5:20fbeb2b391098331cd7dfc08942b9b1	44.3 kB	Download
Supplemental Dataset 32. Lung_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Lung.xlsx md5:50b399c0b3af5a9aa10cff5af760d864	3.9 MB	Download
Supplemental Dataset 33. Lung_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Lung.xlsx md5:d219eb31bb2e97d439cf1836c4b286c7	5.8 MB	Download
Supplemental Dataset 34. Pancreas_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen.xlsx md5:7c906a0c1f69a57e8d89cb57ff4172a8	58.6 kB	Download
Supplemental Dataset 35. Pancreas_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Pancreas.xlsx md5:44730ded33fb7a8a550532b519d25722	4.2 MB	Download
Supplemental Dataset 36. Pancreas_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Pancreas.xlsx md5:431b94b95e9ed1643121e009fef1593f	5.2 MB	Download
Supplemental Dataset 37. Skm_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Skm.xlsx md5:a17d5051111712f39ece4ef7a01401db	42.0 kB	Download
Supplemental Dataset 38. Skm_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Skm.xlsx md5:b7b19251aff40a64a7a638cf9e31ab6e	2.3 MB	Download
Supplemental Dataset 39. Skm_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Skm.xlsx md5:b7e28b3ff42a1c20e9202903f5410e3b	2.7 MB	Download
Supplemental Dataset 4. All Acetyl-Cys Peptide groups _ all columns _ 20220308EKK20220207_Early_Alkylation_TCEPvDTT_PD20220308.xlsx md5:ef5e2f316d0eb7a3ea0e2b19b723c78a	96.2 kB	Download
Supplemental Dataset 40. Spleen_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Spleen.xlsx md5:d390d68fa076adab6daea90fc21656dc	42.4 kB	Download
Supplemental Dataset 41. Spleen_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Spleen.xlsx md5:f066b9786c635805c473577a40619f5d	4.4 MB	Download
Supplemental Dataset 42. Spleen_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Spleen.xlsx md5:6c9b56b524bedc5358fbec274d938776	6.9 MB	Download
Supplemental Dataset 43. Total_ All Acetyl-Cys Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Total.xlsx md5:fe908f0759a02a000a1bc0455f155f33	18.0 kB	Download
Supplemental Dataset 44. Total_ All Peptide groups _ all columns _ 20240104_AcetylCysTissueScreen_Total.xlsx md5:cf76a22f6f141f55fc73c254a26d1544	6.2 MB	Download
Supplemental Dataset 45. Total_ All Proteins _ all columns _ 20240104_AcetylCysTissueScreen_Total.xlsx md5:74e13d393a538b4bd9d5462385083981	7.2 MB	Download
Supplemental Dataset 46. All Acetyl-Cys Peptide groups _ all columns _ 20230212EKK20230126_BAT_4degVsRT_PD20230217.xlsx md5:f24355370f188a71343bd81d409b1c4b	30.9 kB	Download
Supplemental Dataset 47. All Peptide groups _ all columns _ 20230212EKK20230126_BAT_4degVsRT_PD20230217.xlsx md5:762911d6f4aa36a5becfffc8903f01c7	5.3 MB	Download
Supplemental Dataset 48. All Proteins _ all columns _ 20230212EKK20230126_BAT_4degVsRT_PD20230217.xlsx md5:9e96c769f38f56bc0412fab5d7cda370	5.4 MB	Download
Supplemental Dataset 5. All Peptide groups _ all columns _ 20220308EKK20220207_Early_Alkylation_TCEPvDTT_PD20220308.xlsx md5:3e1c46e307ce4991ece58cf9271c199a	15.7 MB	Download
Supplemental Dataset 6. All Proteins _ all columns _ 20220308EKK20220207_Early_Alkylation_TCEPvDTT_PD20220308.xlsx md5:899ddfb7319a9b32dec824908a3654d3	10.0 MB	Download
Supplemental Dataset 7. All Acetyl-Cys Peptide groups _ all columns _ 20221220EKK20220908_Liver+AcetylCoA_PD20220112.xlsx md5:9fdd5480c8b15ff409d6d458b19d5987	161.3 kB	Download
Supplemental Dataset 8. All Peptide groups _ all columns _ 20221220EKK20220908_Liver+AcetylCoA_PD20220112.xlsx md5:696c5974cd4eed91c26c1b811b1e4f5e	21.7 MB	Download
Supplemental Dataset 9. All Proteins _ all columns _ 20221220EKK20220908_Liver+AcetylCoA_PD20220112.xlsx md5:02ac727abb9c04e544e604b94017ee64	11.0 MB	Download
Supplemental Table 1. Acetyl-Cys Peptides_TCEPvDTT.xlsx md5:81f5d44273e545f2edcbfae7edad1047	345.3 kB	Download
Supplemental Table 2. Acetyl-Cys Peptides_EarlyAlkylation.xlsx md5:4875c14044e076c12ff4f4ef6797c426	154.6 kB	Download
Supplemental Table 3. Acetyl-Cys Peptides_Liver+AcetylCoA.xlsx md5:b67e2c3138c1b5fd22e064ef4e6aa597	91.8 kB	Download

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Cysteine S-acetylation is a post-translational modification involved in metabolic regulation

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Files (563.8 MB)