Journal of the American Chemical Society, Vol.131, No.4, 1452-1459, 2009
Chaperonin Complexes Monitored by Ion Mobility Mass Spectrometry
The structural analysis of macromolecular functional protein assemblies by contemporary high resolution structural biology techniques (such as nuclear magnetic resonance, X-ray crystallography, and electron microscopy) is often still challenging. The potential of a rather new method to generate structural information, native mass spectrometry, in combination with ion mobility mass spectrometry (IM-MS), is highlighted here. IM-MS allows the assessment of gas phase ion collision cross sections of protein complex ions, which can be related to overall shapes/volumes of protein assemblies, and thus be used to monitor changes in structure. Here we applied IM-MS to study several (intermediate) chaperonin complexes that can be present during substrate folding. Our results reveal that the protein assemblies retain their solution phase structural properties in the gas phase, addressing a long-standing issue in mass spectrometry. All IM-MS data on the chaperonins point toward the burial of genuine substrates inside the GroEL cavity being retained in the gas phase. Additionally, the overall dimensions of the ternary complexes between GroEL, a substrate, and cochaperonin were found to be similar to the dimensions of the empty GroEL-GroES complex. We also investigated the effect of reducing the charge, obtained in the electrospray process, of the protein complex on the global shape of the chaperonin. At decreased charge, the protein complex was found to be more compact, possibly occupying a lower number of conformational states, enabling an improved ion mobility separation. Charge state reduction was found not to affect the relative differences observed in collision cross sections for the chaperonin assemblies.