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, 35 (12), 1050-5

What Is the Total Number of Protein Molecules Per Cell Volume? A Call to Rethink Some Published Values


What Is the Total Number of Protein Molecules Per Cell Volume? A Call to Rethink Some Published Values

Ron Milo. Bioessays.


Novel methods such as mass-spectrometry enable a view of the proteomes of cells in unprecedented detail. Recently, these efforts have culminated in quantitative measurements of the number of copies per cell for most expressed proteins in organisms ranging from bacteria to mammalian cells. Here, we estimate the expected total number of proteins per unit of cell volume using known parameters related to the composition of cells such as the fraction of cell mass that is protein, and the average protein length. Using simple arguments, we estimate a range of 2-4 million proteins per cubic micron (i.e. 1 fL) in bacteria, yeast, and mammalian cells. Interestingly, we find that measured values that are reported for fission yeast and mammalian cells are often about 3-10 times lower. We discuss this apparent discrepancy and how to use the estimate as benchmark to recalibrate proteome-wide quantitative censuses or to revisit assumptions about cell composition.

Keywords: cell biology by the numbers; mass spectrometry; protein abundance; protein copy numbers; proteins per cell; proteomic calibration; quantitative proteomics.


Figure 1
Figure 1
A back of the envelope calculation of the number of proteins per cell volume. Application for selected model organisms based on their characteristic cell volumes is also given. Estimate is based on generic parameter values. For more accurate organism specific values see main text.

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    1. Sapan CV, Lundblad RL, Price NC. Colorimetric protein assay techniques. Biotechnol Appl Biochem. 1999;29:99–108. - PubMed
    1. Aitken A, Learmonth M. Protein determination by UV absorption. Notes. 2002;205:3–6.
    1. Pedersen S, Bloch PL, Reeh S, Neidhardt FC. Patterns of protein synthesis in E. coli: a catalog of the amount of 140 individual proteins at different growth rates. Cell. 1978;14:179–90. - PubMed
    1. Cox J, Mann M. Quantitative, high-resolution proteomics for data-driven systems biology. Annu Rev Biochem. 2011;80:273–99. - PubMed
    1. Aebersold R, Mann M. Mass spectrometry-based proteomics. Nature. 2003;422:198–207. - PubMed

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