Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling
Abstract Heavy water metabolic labeling followed by liquid chromatography coupled with mass spectrometry is a powerful high throughput technique for measuring the turnover rates of individual proteins in vivo. The turnover rate is obtained from the exponential decay modeling of the depletion of the...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-04-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-023-00873-x |
| _version_ | 1797841132228444160 |
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| author | Henock M. Deberneh Doaa R. Abdelrahman Sunil K. Verma Jennifer J. Linares Andrew J. Murton William K. Russell Muge N. Kuyumcu-Martinez Benjamin F. Miller Rovshan G. Sadygov |
| author_facet | Henock M. Deberneh Doaa R. Abdelrahman Sunil K. Verma Jennifer J. Linares Andrew J. Murton William K. Russell Muge N. Kuyumcu-Martinez Benjamin F. Miller Rovshan G. Sadygov |
| author_sort | Henock M. Deberneh |
| collection | DOAJ |
| description | Abstract Heavy water metabolic labeling followed by liquid chromatography coupled with mass spectrometry is a powerful high throughput technique for measuring the turnover rates of individual proteins in vivo. The turnover rate is obtained from the exponential decay modeling of the depletion of the monoisotopic relative isotope abundance. We provide theoretical formulas for the time course dynamics of six mass isotopomers and use the formulas to introduce a method that utilizes partial isotope profiles, only two mass isotopomers, to compute protein turnover rate. The use of partial isotope profiles alleviates the interferences from co-eluting contaminants in complex proteome mixtures and improves the accuracy of the estimation of label enrichment. In five different datasets, the technique consistently doubles the number of peptides with high goodness-of-fit characteristics of the turnover rate model. We also introduce a software tool, d2ome+, which automates the protein turnover estimation from partial isotope profiles. |
| first_indexed | 2024-04-09T16:26:05Z |
| format | Article |
| id | doaj.art-2fd9fe96ab7f42029f30a4b802d31e12 |
| institution | Directory Open Access Journal |
| issn | 2399-3669 |
| language | English |
| last_indexed | 2024-04-09T16:26:05Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj.art-2fd9fe96ab7f42029f30a4b802d31e122023-04-23T11:11:20ZengNature PortfolioCommunications Chemistry2399-36692023-04-016111210.1038/s42004-023-00873-xQuantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labelingHenock M. Deberneh0Doaa R. Abdelrahman1Sunil K. Verma2Jennifer J. Linares3Andrew J. Murton4William K. Russell5Muge N. Kuyumcu-Martinez6Benjamin F. Miller7Rovshan G. Sadygov8Department of Biochemistry and Molecular Biology, The University of Texas Medical BranchDepartment of Surgery, The University of Texas Medical BranchDepartment of Biochemistry and Molecular Biology, The University of Texas Medical BranchDepartment of Biochemistry and Molecular Biology, The University of Texas Medical BranchDepartment of Surgery, The University of Texas Medical BranchDepartment of Biochemistry and Molecular Biology, The University of Texas Medical BranchDepartment of Biochemistry and Molecular Biology, The University of Texas Medical BranchOklahoma Medical Research Foundation, Oklahoma Nathan Shock Center, Oklahoma Center for Geosciences, Harold Hamm Diabetes CenterDepartment of Biochemistry and Molecular Biology, The University of Texas Medical BranchAbstract Heavy water metabolic labeling followed by liquid chromatography coupled with mass spectrometry is a powerful high throughput technique for measuring the turnover rates of individual proteins in vivo. The turnover rate is obtained from the exponential decay modeling of the depletion of the monoisotopic relative isotope abundance. We provide theoretical formulas for the time course dynamics of six mass isotopomers and use the formulas to introduce a method that utilizes partial isotope profiles, only two mass isotopomers, to compute protein turnover rate. The use of partial isotope profiles alleviates the interferences from co-eluting contaminants in complex proteome mixtures and improves the accuracy of the estimation of label enrichment. In five different datasets, the technique consistently doubles the number of peptides with high goodness-of-fit characteristics of the turnover rate model. We also introduce a software tool, d2ome+, which automates the protein turnover estimation from partial isotope profiles.https://doi.org/10.1038/s42004-023-00873-x |
| spellingShingle | Henock M. Deberneh Doaa R. Abdelrahman Sunil K. Verma Jennifer J. Linares Andrew J. Murton William K. Russell Muge N. Kuyumcu-Martinez Benjamin F. Miller Rovshan G. Sadygov Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling Communications Chemistry |
| title | Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling |
| title_full | Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling |
| title_fullStr | Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling |
| title_full_unstemmed | Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling |
| title_short | Quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling |
| title_sort | quantifying label enrichment from two mass isotopomers increases proteome coverage for in vivo protein turnover using heavy water metabolic labeling |
| url | https://doi.org/10.1038/s42004-023-00873-x |
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