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Proteomics goes global

Nature Biotechnology volume 24, pages 302–303 (2006)Cite this article

But Yates found inspiration rather than despair, exploring how the idea of whole genome sequencing could be applied to the proteome. His team coupled a system of digesting proteins and separating the resulting peptides by cycles of chromatography followed by mass spectrometry in a technique they call MudPIT (multidimensional chromatographic protein identification). With this technique, peptide profiles from heterogeneous mixtures of proteins can be computationally matched with those of known peptides. In 2001, it detected nearly 1,500 distinct proteins in yeast cells, more than anyone had ever seen before in a single analysis1. The previous record, of about 300 proteins, had also been set by the Yates team using the more cumbersome, and less sensitive technique of tandem coupling of two-dimensional liquid chromatography2.

MudPIT could identify many types of proteins that were previously hard to detect. “It was really good at analyzing membrane proteins,” says Yates, “Just digesting them off the lipid bilayer, you could show what proteins were present.” Subsequently, Yates refined techniques to recover more of the membrane proteins and to identify proteins by phosphorylation state and subcellular location3. This ability helped identify 67 previously uncharacterized proteins in the nuclear envelope, several of which mapped to chromosome regions linked with various dystrophies4.

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Proteomics goes global. Nat Biotechnol 24, 302–303 (2006). https://doi.org/10.1038/nbt0306-302

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