Mass spectrometry-based methods for structural biology on a proteome-wide scale

• Published in: Biochemical Society transactions Vol. 48; no. 3; p. 945
• Main Author: Jones, Lisa M
• Format: Journal Article
• Language: English
• Published: England 30.06.2020
• Subjects: Animals; Chromatography, Liquid; Cross-Linking Reagents - chemistry; Disease Models, Animal; Humans; Ligands; Mass Spectrometry - methods; Myocardium - metabolism; Myosins - chemistry; Oxygen - chemistry; Protein Interaction Mapping; Proteins - chemistry; Proteome; Proteomics; Solvents - chemistry; Tandem Mass Spectrometry; protein–protein interactions; mass spectrometry; proteome
• ISSN: 1470-8752
• DOI: 10.1042/BST20190794

Mass spectrometry (MS) has long been used to study proteins mainly via sequence identification and quantitation of expression abundance. In recent years, MS has emerged as a tool for structural biology. Intact protein structural analysis has been enabled by the development of methods such as native MS, top-down proteomics, and ion mobility MS. Other MS-based structural methods include affinity purification MS, chemical cross-linking, and protein footprinting. These methods have enabled the study of protein-protein and protein-ligand interactions and regions of conformational change. The coupling of MS with liquid chromatography has permitted the analysis of complex samples. This bottom-up proteomics workflow enables the study of protein structure in the native cellular environment and provides structural information across the proteome. It has been demonstrated that the crowded environment of the cell affects protein binding interactions and affinities. Performing studies in this complex environment is essential for understanding the functional roles of proteins. MS-based structural methods permit analysis of samples such as cell lysates, intact cells, and tissue to provide a more physiological view of protein structure. This mini-review discusses the various MS-based methods that can be used for proteome-wide structural studies and highlights some of their application.