TY - JOUR

T1 - Lipid-bound ApoE3 self-assemble into elliptical disc-shaped particles

AU - Larsen, Andreas Haahr

AU - Johansen, Nicolai Tidemand

AU - Gajhede, Michael

AU - Arleth, Lise

AU - Midtgaard, Soren Roi

PY - 2021

Y1 - 2021

N2 - 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 (ApoE380-255), which is the central helical repeat segment of ApoE3. The lipid-bound ApoE380-255 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.

AB - 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 (ApoE380-255), which is the central helical repeat segment of ApoE3. The lipid-bound ApoE380-255 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.

KW - Small-angle X-ray scattering, SAXS

KW - High density lipoprotein, HDL

KW - Nanodisc

KW - Apolipoprotein E, ApoE

KW - Lipoprotein

KW - Electron microscopy, EM

KW - HIGH-DENSITY-LIPOPROTEIN

KW - NEGATIVE-STAINING PROTOCOL

KW - HUMAN APOLIPOPROTEIN E3

KW - X-RAY-SCATTERING

KW - NEUTRON-SCATTERING

KW - MEMBRANE-PROTEINS

KW - A-I

KW - CHOLESTEROL

KW - NANODISCS

KW - MODEL

U2 - 10.1016/j.bbamem.2020.183495

DO - 10.1016/j.bbamem.2020.183495

M3 - Journal article

C2 - 33189719

VL - 1863

JO - B B A - Biomembranes

JF - B B A - Biomembranes

SN - 0005-2736

IS - 1

M1 - 183495

ER -