Mass spectrometry analysis of the structural proteome

Mass spectrometry (MS)-based proteomics is moving beyond the simple generation of protein inventories of biological samples. The ability of MS to quantitatively probe complex protein mixtures is increasingly being used to study protein structural and biophysical properties at proteome-scale. MS provides a readout for proteome-wide structural alterations, folding and stability, aggregation, and molecular interactions, all in native-like conditions such as cell lysates or even intact cells. We provide an overview of methods that yield such proteomewide structural information, covering cross-linking-MS, limited proteolysis-MS, co-fractionation-MS, hydroxyl radical footprinting-MS, thermal proteome profiling, and numerous approaches for monitoring molecular interactions at large scale. Methods to determine structural properties of the native proteome will drive structural systems biology.