How many human proteoforms are there?
| Autor: | Michael C. Jewett, Therese Wohlschlager, Vamsi K. Mootha, Jeremy Gunawardena, Steven M. Patrie, James J. Pesavento, Nicolas L. Young, Ole N. Jensen, Catherine Fenselau, Jeffrey N. Agar, Laura L. Kiessling, Sarah A. Slavoff, Evan R. Williams, Sharon J. Pitteri, Emma Lundberg, Lloyd M. Smith, Ruedi Aebersold, Alan Saghatelian, Salvatore Sechi, Marc Vidal, Nathan A. Yates, Tom W. Muir, Michael J. MacCoss, David R. Walt, Parag Mallick, Henry Rodriguez, Jennifer E. Van Eyk, Michael Snyder, Joseph A. Loo, Vicki H. Wysocki, Hartmut Schlüter, Bing Zhang, Milan Mrksich, Benjamin A. Garcia, Martin R. Larsen, Alexander R. Ivanov, Mark S. Baker, Ying Ge, Nevan J. Krogan, Catherine E. Costello, Paul J. Hergenrother, Neil L. Kelleher, I. Jonathan Amster, Rachel R. Ogorzalek Loo, Emily S. Boja, Mathias Uhlén, Benjamin F. Cravatt, Ronald C. Hendrickson, Wendy Sandoval, Paul M. Thomas, Christian G. Huber, Forest M. White, Carolyn R. Bertozzi |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Chemistry, Kiessling, Laura L |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proteomics Biochemistry & Molecular Biology Proteomics methods Molecular composition Proteome 1.1 Normal biological development and functioning Computational biology Biology Genome Article Mass Spectrometry 03 medical and health sciences Databases Medicinal and Biomolecular Chemistry Underpinning research Protein biosynthesis Journal Article Genetics Humans Protein Isoforms Databases Protein Molecular Biology Protein Processing 030102 biochemistry & molecular biology Genome Human Extramural Ubiquitin Protein Post-Translational Proteins Cell Biology Phenotype 030104 developmental biology Post translational Protein Biosynthesis Protein processing Generic health relevance Biochemistry and Cell Biology Protein Processing Post-Translational Human |
| Zdroj: | Nature chemical biology, vol 14, iss 3 Aebersold, R, Agar, J N, Amster, I J, Baker, M S, Bertozzi, C R, Boja, E S, Costello, C E, Cravatt, B F, Fenselau, C, Garcia, B A, Ge, Y, Gunawardena, J, Hendrickson, R C, Hergenrother, P J, Huber, C G, Ivanov, A R, Jensen, O N, Jewett, M C, Kelleher, N L, Kiessling, L L, Krogan, N J, Larsen, M R, Loo, J A, Ogorzalek Loo, R R, Lundberg, E, MacCoss, M J, Mallick, P, Mootha, V K, Mrksich, M, Muir, T W, Patrie, S M, Pesavento, J J, Pitteri, S J, Rodriguez, H, Saghatelian, A, Sandoval, W, Schlüter, H, Sechi, S, Slavoff, S A, Smith, L M, Snyder, M P, Thomas, P M, Uhlén, M, Van Eyk, J E, Vidal, M, Walt, D R, White, F M, Williams, E R, Wohlschlager, T, Wysocki, V H, Yates, N A, Young, N L & Zhang, B 2018, ' How many human proteoforms are there? ', Nature Chemical Biology, vol. 14, no. 3, pp. 206-214 . https://doi.org/10.1038/nchembio.2576 PMC |
| DOI: | 10.1038/nchembio.2576 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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