High-throughput identification of calcium-regulated proteins across diverse proteomes
Open accessPublished version of a preprint
Abstract
Calcium ions play important roles in nearly every biological process, yet whole-proteome analysis of calcium effectors has been hindered by lack of high-throughput, unbiased, and quantitative methods to identify proteins-calcium engagement. To address this, we adapted protein thermostability assays in the budding yeast, human cells, and mouse mitochondria. Based on calcium-dependent thermostability, we identified 2884 putative calcium-regulated proteins across human, mouse, and yeast proteomes. These data revealed calcium engagement of novel signaling hubs and cellular processes, including metabolic enzymes and the spliceosome. Cross-species comparison of calcium-protein engagement and mutagenesis experiments identified residue-specific cation engagement, even within well-known EF-hand domains. Additionally, we found that the dienoyl-CoA reductase DECR1 binds calcium at physiologically-relevant concentrations with substrate-specific affinity, suggesting direct calcium regulation of mitochondrial fatty acid oxidation. These unbiased, proteomic analyses of calcium effectors establish a key resource to dissect cation engagement and its mechanistic effects across multiple species and diverse biological processes.
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Cites
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Highly accurate protein structure prediction with AlphaFold
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Spliceosome Structure and Function
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Tracking cancer drugs in living cells by thermal profiling of the proteome
Savitski, M. M., Reinhard, F. B. M., Franken, H., Werner, T., Savitski, M. F., Eberhard, D., Molina, D. M., Jafari, R., Dovega, R. B., Klaeger, S., et al. (2014) · Science · doi:10.1126/science.1255784 · Cited by 1,187 · see citing works
Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution
Gaetani, M., Sabatier, P., Saei, A. A., Beusch, C. M., Yang, Z., Lundström, S. L., & Zubarev, R. A. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00500 · Cited by 287 · see citing works
Schweppe, D. K., Prasad, S., Belford, M. W., Navarrete-Perea, J., Bailey, D. J., Huguet, R., Jedrychowski, M. P., Rad, R., McAlister, G., Abbatiello, S. E., et al. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05399 · Cited by 229 · see citing works
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- Authors
- Locke, T. M., Fields, R., Gizinski, H., Otto, G. M., MacEwen, M. J. S., Rusnac, D.-V., He, P., Shechner, D. M., McGann, C. D., Berg, M. D., Villen, J., Sancak, Y., & Schweppe, D. K.
- Affiliations
- University of Washington (US)
- Corresponding author
- Sancak, Yasemin
- Schweppe, Devin K.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2024-11
- Volume
- 43
- Issue
- 11
- Pages
- 114879
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC11921809
- OpenAlex
- W4403530186
- Cited by
- 17
- References
- 6
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 1
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R35GM150919-01)
- W. M. Keck Foundation
- Pew Charitable Trusts
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- EF-hand domain, DECR1, mitochondrial fatty acid oxidation, spliceosome, metabolic enzymes, cation binding, cross-species comparison, yeast, human cells
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