Fig. 8: Summary of findings and conclusions.
From: Oligomerization, trans-reduction, and instability of mutant NOTCH3 in inherited vascular dementia
Overall, most mutants demonstrated increased spontaneous instability compared to WT protein, but not all mutants revealed increased instability in all assays tested. Of the assessments of spontaneous instability, multimerization (first row) was observed for all mutants tested. The number of reduced thiols and dynamic instability differed among mutants (second and third rows). The addition of NTF (light blue arc in red box; fourth row), however, induced all mutant proteins into an even less stable state by multiple measures: increased free cysteine labeling visualized by SDS-PAGE gels and MS/MS, increased presence of degradation products identified by IM-MS, and decreased energy requirements for protein unfolding observed by CIU. NTF also altered WT protein but to a lesser degree compared to mutant protein.
