The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy
Författare
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.
Avdelning/ar
- Medical Protein Science
- EXODIAB: Excellence of Diabetes Research in Sweden
Publiceringsår
2013
Språk
Engelska
Sidor
3416-3424
Publikation/Tidskrift/Serie
The FEBS Journal
Volym
280
Issue
14
Dokumenttyp
Artikel i tidskrift
Förlag
Wiley-Blackwell
Ämne
- Biochemistry and Molecular Biology
Nyckelord
- apolipoproteinA-I (ApoA-I)
- cardiovascular
- cholesterol
- EPR
- spectroscopy
- high-density lipoprotein (HDL)
Status
Published
Forskningsgrupp
- Medical Protein Science
ISBN/ISSN/Övrigt
- ISSN: 1742-464X