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Synchrotron radiation circular dichroism spectroscopy reveals structural divergences in HDL-bound apoA-I variants

Giudice, Rita Del LU ; Nilsson, Oktawia LU ; Domingo-Espín, Joan LU and Lagerstedt, Jens O LU (2017) In Scientific Reports 7(1).
Abstract

Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) provides cardiovascular protection. Synchrotron radiation circular dichroism (SRCD) spectroscopy was used to analyze the dynamic solution structure of the apoA-I protein in the apo- and HDL-states and the protein structure conversion in HDL formation. Wild-type apoA-I protein was compared to human variants that either are protective (R173C, Milano) or lead to increased risk for ischaemic heart disease (A164S). Comparable secondary structure distributions in the HDL particles, including significant levels of beta strand/turn, were observed. ApoA-I Milano in HDL displayed larger size heterogeneity, increased protein flexibility, and an altered lipid-binding profile, whereas the... (More)

Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) provides cardiovascular protection. Synchrotron radiation circular dichroism (SRCD) spectroscopy was used to analyze the dynamic solution structure of the apoA-I protein in the apo- and HDL-states and the protein structure conversion in HDL formation. Wild-type apoA-I protein was compared to human variants that either are protective (R173C, Milano) or lead to increased risk for ischaemic heart disease (A164S). Comparable secondary structure distributions in the HDL particles, including significant levels of beta strand/turn, were observed. ApoA-I Milano in HDL displayed larger size heterogeneity, increased protein flexibility, and an altered lipid-binding profile, whereas the apoA-I A164S in HDL showed decrease thermal stability, potentially linking the intrinsic HDL propensities of the variants to disease risk.

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publication status
published
subject
in
Scientific Reports
volume
7
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85040039732
  • wos:000413190900019
ISSN
2045-2322
DOI
10.1038/s41598-017-13878-z
language
English
LU publication?
yes
id
9c427bbf-e48d-404f-aa8d-386a5072b5fd
date added to LUP
2017-11-08 11:16:12
date last changed
2018-02-07 15:03:59
@article{9c427bbf-e48d-404f-aa8d-386a5072b5fd,
  abstract     = {<p>Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) provides cardiovascular protection. Synchrotron radiation circular dichroism (SRCD) spectroscopy was used to analyze the dynamic solution structure of the apoA-I protein in the apo- and HDL-states and the protein structure conversion in HDL formation. Wild-type apoA-I protein was compared to human variants that either are protective (R173C, Milano) or lead to increased risk for ischaemic heart disease (A164S). Comparable secondary structure distributions in the HDL particles, including significant levels of beta strand/turn, were observed. ApoA-I Milano in HDL displayed larger size heterogeneity, increased protein flexibility, and an altered lipid-binding profile, whereas the apoA-I A164S in HDL showed decrease thermal stability, potentially linking the intrinsic HDL propensities of the variants to disease risk.</p>},
  articleno    = {13540},
  author       = {Giudice, Rita Del and Nilsson, Oktawia and Domingo-Espín, Joan and Lagerstedt, Jens O},
  issn         = {2045-2322},
  language     = {eng},
  month        = {10},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Synchrotron radiation circular dichroism spectroscopy reveals structural divergences in HDL-bound apoA-I variants},
  url          = {http://dx.doi.org/10.1038/s41598-017-13878-z},
  volume       = {7},
  year         = {2017},
}