Short Communication - International Research Journal of Biochemistry and Bioinformatics ( 2021) Volume 11, Issue 3
NMR structure determination of the 108kDa discoidal HDL particle - Stefan Bibow - University of Basel, Germany
Stefan Bibow*,
McLeod R A,
Stahlberg H,
Jeschke G,
Guntert P,
Riek R,
Albiez S,
Chi C N,
Polyhach Y,
Kowal J and
Eichmann C
University of Basel, Germany
*Corresponding Author:
Stefan Bibow, University of Basel,
Germany,
Published:
28-Jun-2021
Abstract
High-density lipoprotein particles (HDLs) are
transport containers in the circulatory system that
receive cellular cholesterol and lipids destined for the
liver and other lipoprotein particles. Because low
levels of HDL-cholesterol often indicate an increased
risk for cardiovascular diseases, HDL particles are
considered as important pharmacological targets for
therapeutic strategies. Mature spherical HDLs
develop from lipid-free apolipoprotein apoA-I
through the formation of intermediate discoidal HDL
particles which are the primary acceptors of cellular
cholesterol. Although of high biophysical and
medical importance heterogeneity in density, size,
shape, as well as protein and lipid composition
prohibited a detailed molecular and structural
description of discoidal HDL particles. Here, we
present the three-dimensional solution structure of
reconstituted discoidal HDL (rdHDL) particles by
combining nuclear magnetic resonance (NMR),
electron paramagnetic resonance (EPR) and
transmission electron microscopy (TEM) data.
By using amino acid selective labeling, methyl
labeling, Lipid-PREs and long-range EPR data we
found that rdHDL particles are composed of two
helical apoA-I molecules that dimerise in an antiparallel fashion to form a double belt around a lipid
bilayer patch. The integrity of this unique structure is
maintained by up to 28 salt bridges and an unusual
zipper-like pattern of cation-Ãâ?¬ interactions between
helices 4 and 6. In order to accommodate a
hydrophobic interior a gross ââ?¬ Ë? right to rightââ?¬ â?¢
rotation of the helices upon lipidation is necessary.
The structure relevant in our understanding of HDLbiology and metabolism reflects thereby the beauty
and complexity of this type of biological shuttling
container that is able to hold a fluid lipid/cholesterol
interior at a protein lipid ratio of 1:50.
