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

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Author

  • Jens Lagerstedt
  • Madhu S Budamagunta
  • Grace S Liu
  • Nicole C Devalle
  • John Voss
  • Michael N Oda

Summary, in English

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).

Department/s

Publishing year

2012

Language

English

Pages

448-455

Publication/Series

Biochimica et Biophysica Acta

Volume

1821

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Biological Sciences

Status

Published

Research group

  • Medical Protein Science

ISBN/ISSN/Other

  • ISSN: 0006-3002