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Cited by 28Electron Spin Resonance StudiesProtein Structure and DynamicsLipid Membrane Structure and Behavior

Insight on the Molecular Envelope of Lipid-Bound Apolipoprotein E from Electron Paramagnetic Resonance Spectroscopy

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Hatters, Danny M., Voss, John C., Budamagunta, Madhu S., Newhouse, Yvonne N., Weisgraber, Karl H.·2009·Journal of Molecular Biology
DOI 10.1016/j.jmb.2008.12.040PMC PMC2665048
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Abstract

Although a high-resolution X-ray structure for the N-terminal domain of apolipoprotein E (apoE) in the lipid-free state has been solved, our knowledge of the structure of full-length apoE in a lipid-bound state is limited to an X-ray model fitting a molecular envelope at 10-A resolution. To add molecular detail to the molecular envelope, we used cysteine mutagenesis to incorporate spin labels for analysis with electron paramagnetic resonance (EPR) spectroscopy. Twelve cysteine residues were introduced singly and in pairs at unique locations throughout apoE4 and labeled with an EPR spin probe. The labeled apoE4 was combined with dipalmitoylphosphatidylcholine, the particles were purified, and spectra were determined for 24 combinations (single and double) of the cysteine mutants. Data on the conformation, mobility, distance, and surface exposure of regions revealed by the cysteine probes were modeled into the molecular envelope of apoE bound to dipalmitoylphosphatidylcholine that had been determined by X-ray analysis. This EPR model of apoE in a native lipid-bound state validates the structural model derived from X-ray analysis and provides additional insight into apoE structure-function relationships.

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  • Structural differences among apoE isoforms, especially differences in relative affinities for various apoE receptors, may contribute to differences in Aβ clearance.

    “The impact of structural differences among apoE isoforms (64), especially differences in relative affinities for various apoE receptors, may also contribute to differences in Aβ clearance.”

    From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [64]

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Authors
Hatters, D. M., Voss, J. C., Budamagunta, M. S., Newhouse, Y. N., & Weisgraber, K. H.
Affiliations
  • Gladstone Institutes (US)
  • University of California, Davis (US)
Corresponding author
Weisgraber, Karl H.
ORCID
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2009-02
Volume
386
Issue
1
Pages
261-271
ISSN
0022-2836 (ISSN-L)
DOI
10.1016/j.jmb.2008.12.040
PMC
PMC2665048
OpenAlex
W2051415561
Cited by
28
References
5
Citations by year
2024: 5 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2012: 2
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (R01AG029246, R01AG028793, P01AG022074)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electron Spin Resonance Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
apolipoprotein E, APOE ε4, molecular envelope, DPPC, spin labeling, cysteine mutants, protein-lipid interactions, protein conformation, protein mobility, surface exposure, structure-function relationship
MeSH terms
Apolipoproteins E, Binding Sites, Cysteine, Electron Spin Resonance Spectroscopy, Lipids, Models, Molecular, Protein Conformation, Recombinant Proteins, Spin Labels, 1,2-Dipalmitoylphosphatidylcholine, Mutagenesis, Site-Directed

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