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Cited by 74Mass Spectrometry Techniques and ApplicationsAlzheimer's disease research and treatmentsProtein Structure and Dynamics

Mass spectrometry-based protein footprinting characterizes the structures of oligomeric apolipoprotein E2, E3, and E4

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Gau, Brian, Garai, Kanchan, Frieden, Carl, Gross, Michael L.·2011·Biochemistry
DOI 10.1021/bi200911cPMC PMC3177987
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Abstract

The three common isoforms of apolipoprotein E (ApoE) differ at two sites in their 299 amino acid sequence; these differences modulate the structure of ApoE to affect profoundly the isoform associations with disease. The ε4 allele in particular is strongly associated with Alzheimer's disease. The study of the structural effects of these mutation sites in aqueous media is hampered by the aggregation proclivity of each ApoE isoform. Hence, understanding the differences between isoforms has thus far relied on lower resolution biophysical measurements, mutagenesis, homology studies, and the use of truncated ApoE variants. In this study, we report two comparative studies of the ApoE family by using the mass spectrometry-based protein footprinting methods of FPOP and glycine ethyl ester (GEE) labeling. The first experiment examines the three full-length WT isoforms in their tetrameric state and finds that the overall structures are similar, with the exception of M108 in ApoE4 which is more solvent-accessible in this isoform than in ApoE2 and ApoE3. The second experiment provides clear evidence, from a comparison of the footprinting results of the wild-type proteins and a monomeric mutant, that several residues in regions 183-205 and 232-251 are involved in self-association.

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Authors
Gau, B., Garai, K., Frieden, C., & Gross, M. L.
Affiliations
Washington University in St. Louis (US)
Corresponding author
Gross, Michael L.
ORCID
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
2011-09-02
Volume
50
Issue
38
Pages
8117-8126
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
DOI
10.1021/bi200911c
PMC
PMC3177987
OpenAlex
W2089657004
Cited by
74
References
8
Citations by year
2026: 3 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 8 · 2018: 9 · 2017: 3 · 2016: 7 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 6
FWCI
2.47
Type
journal article
Language
en
Open access
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5p41rr000954-34)
  • National Institute of General Medical Sciences (P41GM103422)
  • National Center for Research Resources (P41-RR000954)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
apolipoprotein E, APOE isoforms, APOE ε4, APOE2, APOE3, protein oligomerization, tetramer structure, protein aggregation, solvent accessibility, self-association, Alzheimer's disease, protein structure
MeSH terms
Amino Acid Sequence, Glycine, Humans, Models, Molecular, Molecular Sequence Data, Recombinant Proteins, Trypsin, Genetic Variation, Mutagenesis, Site-Directed, Crystallography, X-Ray, Amino Acid Substitution, Protein Isoforms, Protein Structure, Quaternary, Protein Footprinting, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2, Tandem Mass Spectrometry, Protein Interaction Domains and Motifs, Photochemical Processes

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