ArticleMolecular & cellular proteomics : MCP2019
Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein.
Article in Molecular & cellular proteomics : MCP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer's disease and related disorders.Molecular neurodegeneration · 2026Review
- The Structural and Functional Journey of Apolipoprotein A-I Through the Human Body.Current atherosclerosis reports · 2026Review
- HDL proteome: from its characterization to quantitative measurements in particle subspecies and functional associations.Expert review of proteomics · 2025Review
- Lecithin:cholesterol acyltransferase binds a discontinuous binding site on adjacent apolipoprotein A-I belts in HDL.Journal of lipid research · 2025Article
- Development of an easy non-destructive particle isolation protocol for quality control of red blood cell concentrates.Journal of extracellular biology · 2025Article
- A Supramolecular Protein Assembly Intrinsically Rescues Memory Deficits in an Alzheimer's Disease Mouse Model.Nano letters · 2024Article
- Article
- Systematic evaluation of lecithin:cholesterol acyltransferase binding sites in apolipoproteins via peptide based nanodiscs: regulatory role of charged residues at positions 4 and 7.PLoS computational biology · 2024Article
- Apolipoprotein E secreted by astrocytes forms antiparallel dimers in discoidal lipoproteins.Neuron · 2024Article
- Flipped C-Terminal Ends of APOA1 Promote ABCA1-Dependent Cholesterol Efflux by Small HDLs.Circulation · 2024Article
- Flipped C-Terminal Ends of APOA1 Promote ABCA1-dependent Cholesterol Efflux by Small HDLs.medRxiv : the preprint server for health sciences · 2023Article
- NMR derived changes of lipoprotein particle concentrations related to impaired fasting glucose, impaired glucose tolerance, or manifest type 2 diabetes mellitus.Lipids in health and disease · 2023Article
- Apolipoprotein Mimetic Peptides: An Emerging Therapy against Diabetic Inflammation and Dyslipidemia.Biomolecules · 2021Review
- Nanodiscs: A toolkit for membrane protein science.Protein science : a publication of the Protein Society · 2021Review
- Probing the structure of nanodiscs using surface-induced dissociation mass spectrometry.Chemical communications (Cambridge, England) · 2020Article
- Cross-linking modifications of HDL apoproteins by oxidized phospholipids: structural characterization,The Journal of biological chemistry · 2020Article
- Structural analysis of lecithin:cholesterol acyltransferase bound to high density lipoprotein particles.Communications biology · 2020Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Apolipoprotein A1 (APOA1), the major protein of high-density lipoprotein (HDL), contains 10 helical repeats that play key roles in protein-protein and protein-lipid interactions. The current structural model for HDL proposes that APOA1 forms an antiparallel dimer in which helix 5 in monomer 1 associates with helix 5 in monomer 2 along a left-left (LL5/5) interface, forming a protein complex with a 2-fold axis of symmetry centered on helix 5. However, computational studies suggest that other orientations are possible. To test this idea, we used a zero-length chemical cross-linking reagent that forms covalent bonds between closely apposed basic and acidic residues. Using proteolytic digestion and tandem mass spectrometry, we identified amino acids in the central region of the antiparallel APOA1 dimer of HDL that were in close contact. As predicted by the current model, we found six intermolecular cross-links that were consistent with the antiparallel LL5/5 registry. However, we also identified three intermolecular cross-links that were consistent with the antiparallel LL5/4 registry. The LL5/5 is the major structural conformation of the two complexes in both reconstituted discoidal HDL particles and in spherical HDL from human plasma. Molecular dynamic simulations suggest that that LL5/5 and LL5/4 APOA1 dimers possess similar free energies of dimerization, with LL5/5 having the lowest free energy. Our observations indicate that phospholipidated APOA1 in HDL forms different antiparallel dimers that could play distinct roles in enzyme regulation, assembly of specific protein complexes, and the functional properties of HDL in humans.
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