Quantitative Aspects of the Human Cell Proteome

Abstract

The number and identity of proteins and proteoforms presented in a single human cell (a cellular proteome) are fundamental biological questions. The answers can be found with sophisticated and sensitive proteomics methods, including advanced mass spectrometry (MS) coupled with separation by gel electrophoresis and chromatography. So far, bioinformatics and experimental approaches have been applied to quantitate the complexity of the human proteome. This review analyzed the quantitative information obtained from several large-scale panoramic experiments in which high-resolution mass spectrometry-based proteomics in combination with liquid chromatography or two-dimensional gel electrophoresis (2DE) were used to evaluate the cellular proteome. It is important that even though all these experiments were performed in different labs using different equipment and calculation algorithms, the main conclusion about the distribution of proteome components (proteins or proteoforms) was basically the same for all human tissues or cells. It follows Zipf’s law and has a formula N = A/x, where N is the number of proteoforms, A is a coefficient, and x is the limit of proteoform detection in terms of abundance.

Puzzle of Proteoform Variety—Where Is a Key?

“…Now, the more challenging task is to decipher the whole proteome’s complexity, including thousands of proteoforms [ 21 ]. This is much more complicated work, as we do not yet know the number of proteoforms in a human proteome [ 2 , 45 ]. We can only make some extrapolations and calculations based on the available data.…”

“…So, it seems that at least one reason for the detection of many proteoforms for some proteins is just their abundance. In favor of this view are the graphs of proteoform abundance inside the cell that follow Zipf’s law [ 45 , 56 ]. But this rule does not work for all proteins.…”