Native Mass Spectrometry, Ion Mobility, Electron-Capture Dissociation, and Modeling Provide Structural Information for Gas-Phase Apolipoprotein E Oligomers.

ABSTRACT: Apolipoprotein E (apoE) is an essential protein in lipid and cholesterol metabolism. Although the three common isoforms in humans differ only at two sites, their consequences in Alzheimer's disease (AD) are dramatically different: only the ε4 allele is a major genetic risk factor for late-onset Alzheimer's disease. The isoforms exist as a mixture of oligomers, primarily tetramer, at low μM concentrations in a lipid-free environment. This self-association is involved in equilibrium with the lipid-free state, and the oligomerization interface overlaps with the lipid-binding region. Elucidation of apoE wild-type (WT) structures at an oligomeric state, however, has not yet been achieved. To address this need, we used native electrospray ionization and mass spectrometry (native MS) coupled with

SUBMITTER: Wang H 

PROVIDER: S-EPMC6504607 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature