In comparison with SA's CIx plot (Figure and S2), SID was a more sensitive diagnostic for isCA than IM. The SID results showed significant shifts, due to post-SID secondary fragmentation, at lower cone voltages than were reflected in the CIx plot. Thus, reliance on IM to determine how harsh the ion source is, and how well the experiment conserved a protein complex's native-like structure, could possibly lead to erroneous conclusions about the true nature of a complex with unknown topology. Additional evidence for quaternary structure rearrangement by isCA is found in Figure , which shows the monomer product's average charge as a function of cone voltage. The statistically significant (*, p < 0.05) increase in average charge state suggests structural rearrangement that allows the monomer to abscond with more charge per mass than is typical under SID conditions. As demonstrated recently, this can happen if the monomer becomes elongated, as typical for CID. Despite the CIx plot showing a decrease in drift time of the tetramer, indicating quaternary structure collapse, the monomer's increasing average charge state suggests that rearrangement involves monomeric expansion. This process is then measured and/or enhanced during SID, allowing for higher charged monomer to result. C-reactive Protein isCA∆ -SIDC. We also examined the 17+ charge state of CRP under the same cone conditions. In contrast to SA, CRP is a cyclic pentamer with a ring-like topology (structure inset in Figure ). The cavity in the middle provides volume for structural rearrangement not available to SA. IsCA clearly induces structural rearrangement (collapse), as seen in the overlay of Figure and, where the drift time starts to decrease at about 100 V. This is 20 -30 V lower than when SA's drift time starts to decrease. Ostensibly, this suggests that SA may possess a more robust quaternary structure than CRP. However, CRP's charge state is higher than SA's, which would result in more energetic in-source ion-neutral collisions during isCA. CRP is also physically larger than SA, causing the pentameric protein to undergo more collisions than SA at the same source pressures. Regardless, isCA clearly induced structural rearrangement in CRP, as we've reported previously, and affected SID trends, as seen in Figure .