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Jens Lagerstedt

Associate professor

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

Author

  • Michael N. Oda
  • Madhu S. Budamagunta
  • Mark S. Borja
  • Jitka Petrlova
  • John C. Voss
  • Jens Lagerstedt

Summary, in English

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.

Department/s

  • Medical Protein Science
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2013

Language

English

Pages

3416-3424

Publication/Series

The FEBS Journal

Volume

280

Issue

14

Document type

Journal article

Publisher

Federation of European Neuroscience Societies and Blackwell Publishing Ltd

Topic

  • Biochemistry and Molecular Biology

Keywords

  • apolipoproteinA-I (ApoA-I)
  • cardiovascular
  • cholesterol
  • EPR
  • spectroscopy
  • high-density lipoprotein (HDL)

Status

Published

Research group

  • Medical Protein Science

ISBN/ISSN/Other

  • ISSN: 1742-464X