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Protein digestion priority is independent of protein abundances

Nature Methods volume 11, pages 220–222 (2014)Cite this article

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To the Editor:

Depletion of high-abundance proteins is an effective way to improve sensitivity in the identification of low-abundance proteins in shotgun proteomics. A recent Brief Communication by Fonslow et al. reported an interesting approach for improving proteome coverage by a method termed digestion and depletion of abundant proteins (DigDeAPr)1. Fonslow et al.1 claimed that their method exploited the abundance-dependent Michaelis-Menten kinetics of trypsin digestion to selectively digest and deplete high-abundance proteins in a two-step digestion process. According to Michaelis-Menten kinetics, the hydrolysis rates for breaking peptide bonds on high-abundance proteins are higher than those for low-abundance proteins (given that the kinetics constants are the same) owing to their higher concentrations. However, Fonslow et al.1 neglected to consider that high-abundance proteins also have high quantities to be consumed by the digestion enzyme. Therefore, higher hydrolysis rates may not lead to their faster consumption in relative concentration (Supplementary Note 1).

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Figure 1: Quantitative proteomics reveals the kinetics of trypsin digestion of proteome sample.

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Acknowledgements

This work is funded in part by the China State Key Basic Research Program Grant (2013CB911202, 2012CB910101, 2012CB910604) and National Natural Science Foundation of China (21321064, 21275142, 21235006).

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Author notes

  1. Mingliang Ye and Yanbo Pan: These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China

    Mingliang Ye, Yanbo Pan, Kai Cheng & Hanfa Zou

  2. University of Chinese Academy of Sciences, Beijing, China

    Mingliang Ye, Yanbo Pan, Kai Cheng & Hanfa Zou

Authors
  1. Mingliang Ye
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  2. Yanbo Pan
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  3. Kai Cheng
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  4. Hanfa Zou
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Corresponding authors

Correspondence to Mingliang Ye or Hanfa Zou.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Figures, Notes and Methods

Supplementary Figures 1 and 2, Supplementary Notes 1–3 and Supplementary Methods (PDF 307 kb)

Supplementary Data

A list of quantified peptides and related information. (XLSX 319 kb)

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Ye, M., Pan, Y., Cheng, K. et al. Protein digestion priority is independent of protein abundances. Nat Methods 11, 220–222 (2014). https://doi.org/10.1038/nmeth.2850

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