Lipid-bound ApoE3 self-assemble into elliptical disc-shaped particles.

Autor: Larsen AH; University of Copenhagen, Niels Bohr Institute, Copenhagen, Denmark; University of Oxford, Department of Biochemistry, Oxford, United Kingdom. Electronic address: andreas.larsen@bioch.ox.ac.uk., Johansen NT; University of Copenhagen, Niels Bohr Institute, Copenhagen, Denmark., Gajhede M; University of Copenhagen, Department of Drug Design and Pharmacology, Copenhagen, Denmark., Arleth L; University of Copenhagen, Niels Bohr Institute, Copenhagen, Denmark. Electronic address: arleth@nbi.ku.dk., Midtgaard SR; University of Copenhagen, Niels Bohr Institute, Copenhagen, Denmark; Boston University School of Medicine, Department of Physiology and Biophysics, Boston, USA.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2021 Jan 01; Vol. 1863 (1), pp. 183495. Date of Electronic Publication: 2020 Nov 13.
DOI: 10.1016/j.bbamem.2020.183495
Abstrakt: Apolipoproteins are vital to lipid metabolism and cholesterol transport in the human body. Here we present a structural study of the lipid-bound particles formed by ApoE3 in a full-length and a truncated version. The particles are formed with, respectively, POPC and DMPC and investigated by small-angle X-ray scattering and negative stain electron microscopy. We find that lipid-bound ApoE3 particles are elliptical, disc-shaped particles composed of a central lipid bilayer encircled by two amphipathic ApoE3 proteins. We went on to investigate a truncated form of ApoE3 containing only residue 80 to 255 (ApoE3 80-255 ), which is the central helical repeat segment of ApoE3. The lipid-bound ApoE3 80-255 particles are found to have the same morphology as the particles with full-length ApoE3. However, they are larger, and form more heterogeneous discoidal structures with four proteins per particle. This behavior is in contrast to ApoA1 where the highly similar helical repeat domain determines the size and stoichiometry of the formed particles both in the case of full-length and truncated ApoA1. Our data hence points towards different mechanisms for lipid bilayer structural modulation by ApoA1 and ApoE3 due to different roles of the non-repeat segments.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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