Mass spectrometric approaches for profiling protein folding and stability

Abstract

Protein stability reports on protein homeostasis, function, and binding interactions, such as to other proteins, metabolites and drugs. As such, there is a pressing need for technologies that can report on protein stability. The ideal technique could be applied in vitro or in vivo systems, proteome-wide, independently of matrix, under native conditions, with residue-level resolution, and on protein at endogenous levels. Mass spectrometry has rapidly become a preferred technology for identifying and quantifying proteins. As such, it has been increasingly incorporated into methodologies for interrogating protein stability and folding. Although no single technology can satisfy all desired applications, several emerging approaches have shown outstanding success at providing biological insight into the stability of the proteome. This chapter outlines some of these recent emerging technologies.

Keywords: Drug binding; Limited proteolysis; Mass spectrometry; Protein folding; Protein footprinting; Protein stability; Proteomics; Thermal protein profiling.