Method sharpens proteome-wide view of structural changes
Protein structure underlies function, and shifts in that structure can reveal changes in cell signaling, metabolism, stress responses and genetic variation. But tracking such structural changes across the proteome remains a challenge. Luise Nagel of the University of Cologne and colleagues in Switzerland developed a method using limited proteolysis coupled with mass spectrometry, or LiP–MS, to distinguish true structural changes from confounding factors such as protein abundance. They published their findings in Molecular & Cellular Proteomics.
LiP–MS works by probing protein structures with proteinase K, or PK, a protease whose digestion patterns shift when proteins change shape. The team validated their method using samples from budding yeast, fission yeast and human cerebrospinal fluid.
To isolate structural signals, they built a framework to remove unwanted variation (RUV) from LiP–MS data. The framework outperformed other approaches by separating structural changes from effects such as protein abundance, posttranslational modifications and alternative splicing. Beyond LiP–MS, the framework could apply to other peptide-centric structural proteomics methods, including fast photochemical oxidation of proteins and molecular painting.
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