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Proteoform: a single term describing protein complexity

Nature Methods volume 10, pages 186–187 (2013) Cite this article

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To the Editor:

A surprise revealed by the success of the human genome project was the lower-than-anticipated number of genes identified: ∼20,300, rather than the ∼100,000 estimated1. This finding led to the recognition that much of the complexity afforded by our biological machinery is at the level of protein variation rather than due to a high number of distinct genes2. The divergences among highly related, but chemically different, protein molecules arise from variation within populations, cell and tissue types and subcellular localization. On the DNA, RNA and protein levels, complexity can arise from allelic variations, from alternative splicing of RNA transcripts and from many post-translational modifications, respectively. These events create distinct protein molecules that modulate a wide variety of biological processes, from cell signaling inside or between cells to gene regulation and activation of protein complexes.

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Figure 1: The origins of the proteoform terminology to cleanly describe biological variability at the level of protein primary structure.

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Acknowledgements

The authors acknowledge the support of the US National Institutes of Health (1R01GM067193 to N.L.K., 1P50HG004952 to L.M.S.) and a grant to N.L.K. from the Chicago Biomedical Consortium, which is supported by the Searle Funds at The Chicago Community Trust. This paper is endorsed by the Consortium for Top Down Proteomics, whose members, including ad hoc members (indicated by an asterisk), at the March 2012 meeting were: Michal Linial, David Goodlett, Pat Langridge-Smith, Young Ah Goo, George Safford, Leo Bonilla*, George Kruppa, Roman Zubarev, Jon Rontree, Julia Chamot-Rooke, John Garavelli, Albert Heck, Joseph Loo, Deborah Penque, Martin Hornshaw, Christopher Hendrickson, Ljiljana Pasa-Tolic, Christoph Borchers, Dominic Chan, Nicholas Young*, Jeffrey Agar, Christophe Masselon, Michael Gross*, Fred McLafferty, Yury Tsybin, Ying Ge, Ian Sanders*, James Langridge, Julian Whitelegge* and Alan Marshall.

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Authors and Affiliations

  1. Department of Chemistry and Genome Center of Wisconsin, University of Wisconsin at Madison, Madison, Wisconsin, USA

    Lloyd M Smith

  2. Department of Chemistry, Northwestern University, Evanston, Illinois, USA

    Neil L Kelleher

  3. Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA

    Neil L Kelleher

  4. Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois, USA

    Neil L Kelleher

Authors
  1. Lloyd M Smith
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  2. Neil L Kelleher
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Consortia

The Consortium for Top Down Proteomics

  • Michal Linial
  • , David Goodlett
  • , Pat Langridge-Smith
  • , Young Ah Goo
  • , George Safford
  • , Leo Bonilla*
  • , George Kruppa
  • , Roman Zubarev
  • , Jon Rontree
  • , Julia Chamot-Rooke
  • , John Garavelli
  • , Albert Heck
  • , Joseph Loo
  • , Deborah Penque
  • , Martin Hornshaw
  • , Christopher Hendrickson
  • , Ljiljana Pasa-Tolic
  • , Christoph Borchers
  • , Dominic Chan
  • , Nicholas Young*
  • , Jeffrey Agar
  • , Christophe Masselon
  • , Michael Gross*
  • , Fred McLafferty
  • , Yury Tsybin
  • , Ying Ge
  • , Ian Sanders*
  • , James Langridge
  • , Julian Whitelegge*
  •  & Alan Marshall

Corresponding author

Correspondence to Neil L Kelleher.

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The authors declare no competing financial interests.

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Smith, L., Kelleher, N. & The Consortium for Top Down Proteomics. Proteoform: a single term describing protein complexity. Nat Methods 10, 186–187 (2013). https://doi.org/10.1038/nmeth.2369

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