Global analysis of bacterial membrane proteins and their modifications

Membrane proteins are situated at the interface of bacterial cell and its environment, and are therefore involved in vital physiological processes such as nutrient exchange, signal transduction and virulence. Due to their distinct biophysical properties, especially hydrophobicity, they are difficult subjects to study. Classical proteomics technologies have relied on multidimensional separation of proteins on gels, which largely limited the choice of detergents and made the development of specialized enrichment protocols for membrane proteins necessary. Shotgun proteomic approaches, based on the digestion of whole proteomes and subsequent analysis of peptides by LC-MS, has largely circumvented these problems due to its compatibility with potent detergents. Here we briefly present and discuss the major developments in bacterial membrane proteomics and argue that recent developments in biochemical sample preparation and high resolution mass spectrometry have the potential to comprehensively identify and quantify membrane proteins without the need for specific enrichment procedures prior to LC-MS analysis.