Synchrotron radiation circular dichroism spectroscopy reveals structural divergences in HDL-bound apoA-I variants
(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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- author
- Giudice, Rita Del LU ; Nilsson, Oktawia LU ; Domingo-Espín, Joan LU and Lagerstedt, Jens O LU
- organization
- publishing date
- 2017-10-19
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 7
- issue
- 1
- article number
- 13540
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85040039732
- wos:000413190900019
- pmid:29051568
- 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
- 2025-01-21 01:30:56
@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>}},
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}},
doi = {{10.1038/s41598-017-13878-z}},
volume = {{7}},
year = {{2017}},
}