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The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy

Oda, Michael N. ; Budamagunta, Madhu S. ; Borja, Mark S. ; Petrlova, Jitka LU ; Voss, John C. and Lagerstedt, Jens LU (2013) In The FEBS Journal 280(14). p.3416-3424
Abstract
ApolipoproteinA-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I... (More)
ApolipoproteinA-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues99-163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues6-98 and 164-238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a -strand (residues149-157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apolipoproteinA-I (ApoA-I), cardiovascular, cholesterol, EPR, spectroscopy, high-density lipoprotein (HDL)
in
The FEBS Journal
volume
280
issue
14
pages
3416 - 3424
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000327128700021
  • scopus:84879902467
  • pmid:23668303
ISSN
1742-464X
DOI
10.1111/febs.12334
language
English
LU publication?
yes
id
f71d810d-85ae-41f2-991a-3ce1caa81562 (old id 4197811)
date added to LUP
2016-04-01 14:38:59
date last changed
2020-03-24 04:06:51
@article{f71d810d-85ae-41f2-991a-3ce1caa81562,
  abstract     = {ApolipoproteinA-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues99-163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues6-98 and 164-238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a -strand (residues149-157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods.},
  author       = {Oda, Michael N. and Budamagunta, Madhu S. and Borja, Mark S. and Petrlova, Jitka and Voss, John C. and Lagerstedt, Jens},
  issn         = {1742-464X},
  language     = {eng},
  number       = {14},
  pages        = {3416--3424},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {The FEBS Journal},
  title        = {The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy},
  url          = {http://dx.doi.org/10.1111/febs.12334},
  doi          = {10.1111/febs.12334},
  volume       = {280},
  year         = {2013},
}