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Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans
Open accessAbstract
Mass-spectrometry-based methods for relative proteome quantification have broadly affected life science research. However, important research directions, particularly those involving mathematical modelling and simulation of biological processes, also critically depend on absolutely quantitative data--that is, knowledge of the concentration of the expressed proteins as a function of cellular state. Until now, absolute protein concentration measurements of a considerable fraction of the proteome (73%) have only been derived from genetically altered Saccharomyces cerevisiae cells, a technique that is not directly portable from yeast to other species. Here we present a mass-spectrometry-based strategy to determine the absolute quantity, that is, the average number of protein copies per cell in a cell population, for a large fraction of the proteome in genetically unperturbed cells. Applying the technology to the human pathogen Leptospira interrogans, a spirochete responsible for leptospirosis, we generated an absolute protein abundance scale for 83% of the mass-spectrometry-detectable proteome, from cells at different states. Taking advantage of the unique cellular dimensions of L. interrogans, we used cryo-electron tomography morphological measurements to verify, at the single-cell level, the average absolute abundance values of selected proteins determined by mass spectrometry on a population of cells. Because the strategy is relatively fast and applicable to any cell type, we expect that it will become a cornerstone of quantitative biology and systems biology.
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In the citing paper
“Tissue-specific amino acid precursor pools and recycling rates, a pervasive problem for in vivo pulse labeling experiments 15,22 , did not appreciably affect our results (Fig. S1).”
From Global quantification of mammalian gene expression control (2011) · cites this paper as [22]
Experimental — accuracy not yet measuredIn the citing paper
“Mass spectrometry (MS)-based methods can overcome these difficulties and were recently used to determine protein copy numbers per cell for a significant fraction of the proteome of two bacterial species, namely Mycoplasma pneumonia and Leptospira interrogans (Malmstrom et al, 2009; Maier et al, 2011) and yeast (de Godoy et al, 2008).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
In the citing paper
“We used the same data to calculate three different protein abundance scores as previously described (Ishihama et al, 2005; Silva et al, 2006; Malmstrom et al, 2009) and validated their precision by statistical analysis (Supplementary Figure S1; see Supplementary information for detail).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
In the citing paper
“We and others have previously shown that the dynamic range of protein concentrations spans more than three orders of magnitude in the bacterium L. interrogans (Malmstrom et al, 2009) and five orders of magnitude in yeast (Ghaemmaghami et al, 2003; de Godoy et al, 2008; Picotti et al, 2009).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
In the citing paper
“Those proteins make up the majority of the total protein mass (Malmstrom et al, 2009) and a considerable fraction of the cytoplasmic volume (Beck et al, 2009), while proteins functioning in signaling, protein transport, or regulatory pathways, e.g. transcription factors, comprise a minority of the quantitative proteome.”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
In the citing paper
“Interestingly, the bacterium L. interrogans expresses a relatively small number of in very high copy proteins, e.g. proteins of the translation and protein folding system, metabolic enzymes as well as components of the cell wall.”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
In the citing paper
“The arbitrary protein abundance indices were calibrated to absolute protein copy numbers per cell their precision validated by bootstrapping analysis as described earlier (Malmstrom et al, 2009).”
From The quantitative proteome of a human cell line (2011) · cites this paper as Malmstrom et al, 2009
In the citing paper
“The MS signal of peptides identifying each protein can be used to estimate its absolute cellular abundance (de Godoy et al, 2008; Malmstrom et al, 2009; Silva et al, 2006)”
From Deep proteome and transcriptome mapping of a human cancer cell line (2011) · cites this paper as Malmstrom et al, 2009
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Metadata
- Authors
- Malmström, J., Beck, M., Schmidt, A., Lange, V., Deutsch, E. W., & Aebersold, R.
- Affiliations
- ETH Zurich (CH)
- Institute for Systems Biology (US)
- University of Zurich (CH)
- Corresponding author
- Aebersold, Ruedi
- Venue
- Nature
- Published
- 2009-07-15
- Volume
- 460
- Issue
- 7256
- Pages
- 762-765
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2723184
- OpenAlex
- W2041852635
- Cited by
- 421
- References
- 33
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 11 · 2020: 17 · 2019: 17 · 2018: 28 · 2017: 20 · 2016: 28 · 2015: 23 · 2014: 35 · 2013: 37 · 2012: 60
- FWCI
- 23.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health (n01hv28179-12-0-0)
- National Heart, Lung, and Blood Institute (N01 HV028179, N01-HV-28179)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › Leptospirosis research and findings
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- Leptospira interrogans, protein copy number, leptospirosis, cryo-electron tomography, quantitative proteomics, spirochetes
- MeSH terms
- Bacterial Proteins, Chromatography, High Pressure Liquid, Chromatography, Liquid, Humans, Leptospira interrogans, Mass Spectrometry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cryoelectron Microscopy, Proteome, Proteomics, Tandem Mass Spectrometry, Electron Microscope Tomography
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