title: Solution structure of discoidal high-density lipoprotein particles with a shortened apolipoprotein A-I.
abstract: High-density lipoprotein (HDL) particles are cholesterol and lipid transport containers. Mature HDL particles destined for the liver develop through the formation of intermediate discoidal HDL particles, which are the primary acceptors for cholesterol. Here we present the three-dimensional structure of reconstituted discoidal HDL (rdHDL) particles, using a shortened construct of human apolipoprotein A-I, determined from a combination of nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and transmission electron microscopy (TEM) data. The rdHDL particles feature a protein double belt surrounding a lipid bilayer patch in an antiparallel fashion. The integrity of this structure is maintained by up to 28 salt bridges and a zipper-like pattern of cation-π interactions between helices 4 and 6. To accommodate a hydrophobic interior, a gross 'right-to-right' rotation of the helices after lipidation is necessary. The structure reflects the complexity required for a shuttling container to hold a fluid lipid or cholesterol interior at a protein:lipid ratio of 1:50.
authors.affiliation: Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bibow
authors.affiliation: Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Yevhen
authors.initials: Y
authors.lastname: Polyhach
authors.affiliation: Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Eichmann
authors.affiliation: Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Celestine N
authors.identifier: 0000-0003-4154-2378
authors.initials: CN
authors.lastname: Chi
authors.affiliation: Center for Cellular Imaging and NanoAnalytics, Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Kowal
authors.affiliation: Center for Cellular Imaging and NanoAnalytics, Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Albiez
authors.affiliation: Center for Cellular Imaging and NanoAnalytics, Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Robert A
authors.initials: RA
authors.lastname: McLeod
authors.affiliation: Center for Cellular Imaging and NanoAnalytics, Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Henning
authors.identifier: 0000-0002-1185-4592
authors.initials: H
authors.lastname: Stahlberg
authors.affiliation: Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jeschke
authors.affiliation: Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.|Institute of Biophysical Chemistry, Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Güntert
authors.affiliation: Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D000072756:Protein Conformation, alpha-Helical; D017433:Protein Structure, Secondary; D012996:Solutions
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D012996:Solutions