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The "beta-clasp" model of apolipoprotein A-I - A lipid-free solution structure determined by electron paramagnetic resonance spectroscopy.

Lagerstedt, Jens LU ; Budamagunta, Madhu S; Liu, Grace S; Devalle, Nicole C; Voss, John LU and Oda, Michael N (2012) In Biochimica et Biophysica Acta 1821(3). p.448-455
Abstract
Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and plays a central role in cholesterol metabolism. The lipid-free/lipid-poor form of apoA-I is the preferred substrate for the ATP-binding cassette transporter A1 (ABCA1). The interaction of apoA-I with ABCA1 leads to the formation of cholesterol laden high density lipoprotein (HDL) particles, a key step in reverse cholesterol transport and the maintenance of cholesterol homeostasis. Knowledge of the structure of lipid-free apoA-I is essential to understanding its critical interaction with ABCA1 and the molecular mechanisms underlying HDL biogenesis. We therefore examined the structure of lipid-free apoA-I by electron paramagnetic resonance... (More)
Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and plays a central role in cholesterol metabolism. The lipid-free/lipid-poor form of apoA-I is the preferred substrate for the ATP-binding cassette transporter A1 (ABCA1). The interaction of apoA-I with ABCA1 leads to the formation of cholesterol laden high density lipoprotein (HDL) particles, a key step in reverse cholesterol transport and the maintenance of cholesterol homeostasis. Knowledge of the structure of lipid-free apoA-I is essential to understanding its critical interaction with ABCA1 and the molecular mechanisms underlying HDL biogenesis. We therefore examined the structure of lipid-free apoA-I by electron paramagnetic resonance spectroscopy (EPR). Through site directed spin label EPR, we mapped the secondary structure of apoA-I and identified sites of spin coupling as residues 26, 44, 64, 167, 217 and 226. We capitalize on the fact that lipid-free apoA-I self-associates in an anti-parallel manner in solution. We employed these sites of spin coupling to define the central plane in the dimeric apoA-I complex. Applying both the constraints of dipolar coupling with the EPR-derived pattern of solvent accessibility, we assembled the secondary structure into a tertiary context, providing a solution structure for lipid-free apoA-I. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochimica et Biophysica Acta
volume
1821
issue
3
pages
448 - 455
publisher
Elsevier
external identifiers
  • WOS:000301820400013
  • PMID:22245143
  • Scopus:84862785850
ISSN
0006-3002
DOI
10.1016/j.bbalip.2011.12.010
language
English
LU publication?
yes
id
1db5b168-22ba-4340-9319-47a6922848ad (old id 2336426)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22245143?dopt=Abstract
date added to LUP
2012-02-01 21:06:55
date last changed
2016-10-13 04:34:17
@misc{1db5b168-22ba-4340-9319-47a6922848ad,
  abstract     = {Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and plays a central role in cholesterol metabolism. The lipid-free/lipid-poor form of apoA-I is the preferred substrate for the ATP-binding cassette transporter A1 (ABCA1). The interaction of apoA-I with ABCA1 leads to the formation of cholesterol laden high density lipoprotein (HDL) particles, a key step in reverse cholesterol transport and the maintenance of cholesterol homeostasis. Knowledge of the structure of lipid-free apoA-I is essential to understanding its critical interaction with ABCA1 and the molecular mechanisms underlying HDL biogenesis. We therefore examined the structure of lipid-free apoA-I by electron paramagnetic resonance spectroscopy (EPR). Through site directed spin label EPR, we mapped the secondary structure of apoA-I and identified sites of spin coupling as residues 26, 44, 64, 167, 217 and 226. We capitalize on the fact that lipid-free apoA-I self-associates in an anti-parallel manner in solution. We employed these sites of spin coupling to define the central plane in the dimeric apoA-I complex. Applying both the constraints of dipolar coupling with the EPR-derived pattern of solvent accessibility, we assembled the secondary structure into a tertiary context, providing a solution structure for lipid-free apoA-I. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).},
  author       = {Lagerstedt, Jens and Budamagunta, Madhu S and Liu, Grace S and Devalle, Nicole C and Voss, John and Oda, Michael N},
  issn         = {0006-3002},
  language     = {eng},
  number       = {3},
  pages        = {448--455},
  publisher    = {ARRAY(0xb3f48a0)},
  series       = {Biochimica et Biophysica Acta},
  title        = {The "beta-clasp" model of apolipoprotein A-I - A lipid-free solution structure determined by electron paramagnetic resonance spectroscopy.},
  url          = {http://dx.doi.org/10.1016/j.bbalip.2011.12.010},
  volume       = {1821},
  year         = {2012},
}