Investigation of D76N β₂-Microglobulin Using Protein Footprinting and Structural Mass Spectrometry.

ABSTRACT: NMR studies and X-ray crystallography have shown that the structures of the 99-residue amyloidogenic protein β₂-microglobulin (β₂m) and its more aggregation-prone variant, D76N, are indistinguishable, and hence, the reason for the striking difference in their aggregation propensities remains elusive. Here, we have employed two protein footprinting methods, hydrogen-deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP), in conjunction with ion mobility-mass spectrometry, to probe the differences in conformational dynamics of the two proteins. Using HDX-MS, a clear difference in HDX protection is observed between these two proteins in the E-F loop (residues 70-77) which contains the D76N substitution, with a significantly higher deuterium uptake b

SUBMITTER: Cornwell O 

PROVIDER: S-EPMC9282677 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature