How many human proteoforms are there?
Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2019
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| Online Access: | http://hdl.handle.net/1721.1/120977 https://orcid.org/0000-0001-6829-1500 |
| _version_ | 1826200014914846720 |
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| author | Aebersold, Ruedi Agar, Jeffrey N Amster, I Jonathan Baker, Mark S Bertozzi, Carolyn R Boja, Emily S Costello, Catherine E Cravatt, Benjamin F Fenselau, Catherine Garcia, Benjamin A Ge, Ying Gunawardena, Jeremy Hendrickson, Ronald C Hergenrother, Paul J Huber, Christian G Ivanov, Alexander R Jensen, Ole N Jewett, Michael C Kelleher, Neil L Krogan, Nevan J Larsen, Martin R Loo, Joseph A Ogorzalek Loo, Rachel R Lundberg, Emma MacCoss, Michael J Mallick, Parag Mootha, Vamsi K Mrksich, Milan Muir, Tom W Patrie, Steven M Pesavento, James J Pitteri, Sharon J Rodriguez, Henry Saghatelian, Alan Sandoval, Wendy Schlüter, Hartmut Sechi, Salvatore Slavoff, Sarah A Smith, Lloyd M Snyder, Michael P Thomas, Paul M Uhlén, Mathias Van Eyk, Jennifer E Vidal, Marc Walt, David R White, Forest M Williams, Evan R Wohlschlager, Therese Wysocki, Vicki H Yates, Nathan A Young, Nicolas L Zhang, Bing Kiessling, Laura L |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Aebersold, Ruedi Agar, Jeffrey N Amster, I Jonathan Baker, Mark S Bertozzi, Carolyn R Boja, Emily S Costello, Catherine E Cravatt, Benjamin F Fenselau, Catherine Garcia, Benjamin A Ge, Ying Gunawardena, Jeremy Hendrickson, Ronald C Hergenrother, Paul J Huber, Christian G Ivanov, Alexander R Jensen, Ole N Jewett, Michael C Kelleher, Neil L Krogan, Nevan J Larsen, Martin R Loo, Joseph A Ogorzalek Loo, Rachel R Lundberg, Emma MacCoss, Michael J Mallick, Parag Mootha, Vamsi K Mrksich, Milan Muir, Tom W Patrie, Steven M Pesavento, James J Pitteri, Sharon J Rodriguez, Henry Saghatelian, Alan Sandoval, Wendy Schlüter, Hartmut Sechi, Salvatore Slavoff, Sarah A Smith, Lloyd M Snyder, Michael P Thomas, Paul M Uhlén, Mathias Van Eyk, Jennifer E Vidal, Marc Walt, David R White, Forest M Williams, Evan R Wohlschlager, Therese Wysocki, Vicki H Yates, Nathan A Young, Nicolas L Zhang, Bing Kiessling, Laura L |
| author_sort | Aebersold, Ruedi |
| collection | MIT |
| description | Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype. |
| first_indexed | 2024-09-23T11:29:29Z |
| format | Article |
| id | mit-1721.1/120977 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:29:29Z |
| publishDate | 2019 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1209772022-09-27T19:55:21Z How many human proteoforms are there? Aebersold, Ruedi Agar, Jeffrey N Amster, I Jonathan Baker, Mark S Bertozzi, Carolyn R Boja, Emily S Costello, Catherine E Cravatt, Benjamin F Fenselau, Catherine Garcia, Benjamin A Ge, Ying Gunawardena, Jeremy Hendrickson, Ronald C Hergenrother, Paul J Huber, Christian G Ivanov, Alexander R Jensen, Ole N Jewett, Michael C Kelleher, Neil L Krogan, Nevan J Larsen, Martin R Loo, Joseph A Ogorzalek Loo, Rachel R Lundberg, Emma MacCoss, Michael J Mallick, Parag Mootha, Vamsi K Mrksich, Milan Muir, Tom W Patrie, Steven M Pesavento, James J Pitteri, Sharon J Rodriguez, Henry Saghatelian, Alan Sandoval, Wendy Schlüter, Hartmut Sechi, Salvatore Slavoff, Sarah A Smith, Lloyd M Snyder, Michael P Thomas, Paul M Uhlén, Mathias Van Eyk, Jennifer E Vidal, Marc Walt, David R White, Forest M Williams, Evan R Wohlschlager, Therese Wysocki, Vicki H Yates, Nathan A Young, Nicolas L Zhang, Bing Kiessling, Laura L Massachusetts Institute of Technology. Department of Chemistry Kiessling, Laura L Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype. 2019-03-15T13:22:11Z 2019-03-15T13:22:11Z 2018-02 2017-12 2019-03-15T12:45:24Z Article http://purl.org/eprint/type/JournalArticle 1552-4450 1552-4469 http://hdl.handle.net/1721.1/120977 Aebersold, Ruedi et al. “How Many Human Proteoforms Are There?” Nature Chemical Biology 14, 3 (February 2018): 206–214 © 2018 Nature Publishing Group https://orcid.org/0000-0001-6829-1500 http://dx.doi.org/10.1038/NCHEMBIO.2576 Nature Chemical Biology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Aebersold, Ruedi Agar, Jeffrey N Amster, I Jonathan Baker, Mark S Bertozzi, Carolyn R Boja, Emily S Costello, Catherine E Cravatt, Benjamin F Fenselau, Catherine Garcia, Benjamin A Ge, Ying Gunawardena, Jeremy Hendrickson, Ronald C Hergenrother, Paul J Huber, Christian G Ivanov, Alexander R Jensen, Ole N Jewett, Michael C Kelleher, Neil L Krogan, Nevan J Larsen, Martin R Loo, Joseph A Ogorzalek Loo, Rachel R Lundberg, Emma MacCoss, Michael J Mallick, Parag Mootha, Vamsi K Mrksich, Milan Muir, Tom W Patrie, Steven M Pesavento, James J Pitteri, Sharon J Rodriguez, Henry Saghatelian, Alan Sandoval, Wendy Schlüter, Hartmut Sechi, Salvatore Slavoff, Sarah A Smith, Lloyd M Snyder, Michael P Thomas, Paul M Uhlén, Mathias Van Eyk, Jennifer E Vidal, Marc Walt, David R White, Forest M Williams, Evan R Wohlschlager, Therese Wysocki, Vicki H Yates, Nathan A Young, Nicolas L Zhang, Bing Kiessling, Laura L How many human proteoforms are there? |
| title | How many human proteoforms are there? |
| title_full | How many human proteoforms are there? |
| title_fullStr | How many human proteoforms are there? |
| title_full_unstemmed | How many human proteoforms are there? |
| title_short | How many human proteoforms are there? |
| title_sort | how many human proteoforms are there |
| url | http://hdl.handle.net/1721.1/120977 https://orcid.org/0000-0001-6829-1500 |
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