ArticleProtein and peptide letters2016
Mechanism of Lipid Binding of Human Apolipoprotein E3 by Hydrogen/Deuterium Exchange/Mass Spectrometry and Fluorescence Polarization.
Article in Protein and peptide letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Conformational features of guinea pig apolipoprotein E offer insights into functioning of human apolipoprotein E.Archives of biochemistry and biophysics · 2025Article
- The role of C-terminal ionic residues in self-association of apolipoprotein A-I.Biochimica et biophysica acta. Biomembranes · 2023Article
- Insights into the C-terminal domain of apolipoprotein E from chimera studies with apolipophorin III.Molecular and cellular biochemistry · 2023Article
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- The LDL receptor binding domain of apolipoprotein E directs the relative orientation of its C-terminal segment in reconstituted nascent HDL.Biochimica et biophysica acta. Biomembranes · 2021Article
- Protein oligomerization as a metabolic control mechanism: Application to apoE.Protein science : a publication of the Protein Society · 2019Article
- Ordered opening of LDL receptor binding domain of human apolipoprotein E3 revealed by hydrogen/deuterium exchange mass spectrometry and fluorescence spectroscopy.Biochimica et biophysica acta. Proteins and proteomics · 2018Article
- Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Swapping the N- and C-terminal domains of human apolipoprotein E3 and AI reveals insights into their structure/activity relationship.PloS one · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHuman apolipoprotein E3 (apoE3) is an exchangeable apolipoprotein that plays a critical role in maintaining plasma cholesterol/triglyceride homeostasis. The C-terminal (CT) domain of apoE3 (residues 201-299) is composed of amphipathic α-helices C1: W210-S223, C2: V236-E266, and C3: D271-W276, which play a dominant role in mediating high-affinity lipid binding.
objectiveThe objective is to understand the accessibility of the CT domain at the sub-domain level and the mechanistic details regarding lipid-binding interaction.
methodsHydrogen-deuterium exchange coupled to mass spectrometry (HDX/MS) of recombinant wild type (WT) apoE(201-299), chemical-induced unfolding monitored as changes in fluorescence polarization (FP) of labeled apoE(201-299) bearing a probe at specified sites, and lipid binding studies were carried out.
resultsHDX/MS revealed that residues towards the C-terminal end of the domain display significantly lower %D uptake compared to those towards the center, suggesting extensive protein-protein interaction in this segment. Functional assays showed that locking apoE(201-299) in an inter-molecular disulfide-bonded state at position 209, 223, 255, or 277 significantly decreases its ability to interact with lipids, especially when tethered towards the ends; this could be restored by reduction. Unfolding studies indicate that the C-terminal end offers less resistance to unfolding compared to the central portion of the domain.
conclusionTaken together, our data suggest that two dimers of CT domain are juxtaposed around helix C3 leading to apoE3 tetramerization, and that dissociation to monomeric units is a required step in lipid binding, with helix C3 likely seeking stability via lipid interaction prior to helices C1 or C2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.