The "beta-clasp" model of apolipoprotein A-I - A lipid-free solution structure determined by electron paramagnetic resonance spectroscopy.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2336426
- author
- Lagerstedt, Jens LU ; Budamagunta, Madhu S ; Liu, Grace S ; Devalle, Nicole C ; Voss, John LU and Oda, Michael N
- organization
- publishing date
- 2012
- 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
- pmid:22245143
- 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
- 2016-04-04 09:38:19
- date last changed
- 2022-01-29 18:48:51
@article{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 = {{Elsevier}}, 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}}, doi = {{10.1016/j.bbalip.2011.12.010}}, volume = {{1821}}, year = {{2012}}, }