Tandem mass spectrometry of integral membrane proteins for top-down proteomics

Transmembrane domains of integral membrane proteins present a formidable analytical challenge due to their general lack of polarity; recovery is enhanced by maintaining their association with polar-loop regions. Multi-dimensional separations of intact integral membrane proteins coupled with high-resolution electrospray-ionization mass spectrometers enable “top-down” proteomics, with coverage of bilayer domains.