Figure 3.
Timeline of MS-based analyses of macromolecular complexes. The advent of ESI127,160 and of nano-ESI161 laid the groundwork for native MS. In 1991 the first examples of the analysis of macromolecular complexes were published and in 1998 electron capture dissociation (ECD) was developed.74 In 2002 John Bennett Fenn was awarded a share of the Nobel Prize in Chemistry for his contribution to the development of electrospray ionization. In the same year noncovalent complexes were fragmented by ECD76 and tandem MS (i.e., MS2) experiments of protein complexes were performed.32 In 2006 ECD fragmentation of a ligand−protein complex was first reported.80 Subsequently, intact protein complexes were fragmented by ECD121 and in 2013 subunits ejected from intact protein complexes were broken down using MS3 experiments.131