Trifluoroethanol Partially Unfolds G93A SOD1 Leading to Protein Aggregation: A Study by Native Mass Spectrometry and FPOP Protein Footprinting

• DOI: 10.1021/acs.biochem.0c00425
• Publication Date: 2020-09-14T10:38:45Z
• Authors: Ben Niu; Brian C. Mackness; Jill A. Zitzewitz; C. Robert Matthews; Michael L. Gross
• Keywords: Footprinting

Misfolding of Cu, Zn superoxide dismutase (SOD1) variants may lead to protein aggregation and ultimately amyotrophic lateral sclerosis (ALS). The mechanism conformational changes during this process are complex remain unclear. To study SOD1 variant at the molecular level in solution, we chemically induced a mutant (G93A SOD1) with trifluoroethanol (TFE) used both native mass spectrometry (MS) analyze intact fast photochemical oxidation proteins (FPOP) characterize structural by TFE. We found partially unfolded G93A monomers prior oligomerization identified regions N-terminus, C-terminus, strands β5, β6 accountable for partial unfolding. propose that exposure hydrophobic interfaces these unstructured serves as precursor aggregation. Our results provide possible basis ALS-linked misfolding