- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
- Cell death mechanisms and regulation
- RNA regulation and disease
Brigham Young University
2022-2024
Abstract The p97 AAA+ATPase is an essential and abundant regulator of protein homeostasis that plays a central role in unfolding ubiquitylated substrates. Here we report two cryo-EM structures human complex with its p47 adaptor. One the conformations six-fold symmetric, corresponds to previously reported p97, lacks bound substrate. other structure adopts helical conformation, displays substrate running extended conformation through pore hexamer, resembles for AAA unfoldases. These findings...
Apolipoprotein E (ApoE) polymorphisms modify the risk of Alzheimer’s disease with ApoE4 strongly increasing and ApoE2 modestly decreasing relative to control ApoE3. To investigate how ApoE isoforms alter risk, we measured changes in proteome homeostasis transgenic mice expressing a human gene (isoform 2, 3, or 4). The regulation each protein’s is observed by measuring turnover rate abundance for that protein. We identified 4849 proteins tested isoform-dependent homeostatic ~2700 ontologies....
ABSTRACT Apolipoprotein E (ApoE) polymorphisms modify the risk of neurodegenerative disease with ApoE4 isoform increasing and ApoE2 decreasing relative to ‘wild-type control’ ApoE3 isoform. To elucidate how ApoE isoforms alter proteome, we measured protein abundance turnover in transgenic mice expressing a human gene (isoform 2, 3, or 4). This data provides insight into affect vivo synthesis degradation wide variety proteins. We identified 4849 proteins tested for isoform-dependent changes...