High-sensitivity Orbitrap mass analysis of intact macromolecular assemblies

Modifications to an Orbitrap-based mass spectrometer enable analysis of large protein complexes in native-like states by mass spectrometry with very high sensitivity and mass resolution. The analysis of intact protein assemblies in native-like states by mass spectrometry offers a wealth of information on their biochemical and biophysical properties. Here we show that the Orbitrap mass analyzer can be used to measure protein assemblies of molecular weights approaching one megadalton with sensitivity down to the detection of single ions. Minor instrumental modifications enabled the measurement of various protein assemblies with outstanding mass-spectral resolution.