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Proteomics

Proteoforms feel the heat

Nature Chemical Biology (2023)Cite this article

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Identifying new proteoforms — structural variants of proteins — is frequently challenging, particularly on the proteome-wide scale. A new study leverages their differential thermal stabilities to identify proteoform functional groups by deep thermal proteome profiling.

The proteomics field is broadly divided by two approaches: top-down and bottom-up. In bottom-up proteomics, proteins are digested into peptides prior to separation and analysis by liquid chromatography tandem mass spectrometry. The presence and modification state of proteins are then inferred based on peptide measurements. Top-down proteomics involves ionization of intact proteins and characterizes combinations of modifications3. Owing to its greater robustness, depth of coverage and access to larger proteins, bottom-up proteomics has achieved wider adoption of the two but is rarely capable of delivering proteoform-resolved measurements. Substantial effort has been expended to improve the confidence of proteoform inference from bottom-up proteomics experiments with the greatest focus on peptide correlative analysis4,5. These techniques correlate changes in peptide abundance across biological contexts to detect proteoforms. These incidental changes in peptide abundance are not tightly connected to the structural state of a protein, so they could be improved with such a measurement.

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Fig. 1: Structural variations of proteoforms influence thermal stability.

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  1. Department of Chemistry Purdue University, West Lafayette, IN, USA

    Teagan L. Campbell & Bryon S. Drown

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  1. Teagan L. Campbell
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  2. Bryon S. Drown
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Correspondence to Bryon S. Drown.

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The authors declare no competing interests.

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Campbell, T.L., Drown, B.S. Proteoforms feel the heat. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01285-7

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  • DOI: https://doi.org/10.1038/s41589-023-01285-7

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