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The secondary structure of apolipoprotein A ‐ I on 9.6‐nm reconstituted high‐density lipoprotein determined by EPR spectroscopy
Author(s) -
Oda Michael N.,
Budamagunta Madhu S.,
Borja Mark S.,
Petrlova Jitka,
Voss John C.,
Lagerstedt Jens O.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12334
Subject(s) - chemistry , apolipoprotein b , electron paramagnetic resonance , lipoprotein , cholesterol , high density lipoprotein , context (archaeology) , protein structure , biochemistry , nuclear magnetic resonance spectroscopy , crystallography , biophysics , stereochemistry , biology , nuclear magnetic resonance , physics , paleontology
Apolipoprotein A ‐ I ( A po A ‐ 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 A po A ‐ 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 A po A ‐ 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 A po A ‐ I central domain on HDL . The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of A po A ‐ I residues 99–163 on 9.6‐nm reconstituted HDL was analyzed by EPR . In previous analyses, we examined residues 6–98 and 164–238 (of A po A ‐ 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 A po A ‐ I . Remarkably, given that the majority of A po A ‐ I 's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a β‐strand (residues 149–157). The significance of these nonhelical residues is discussed, along with the other features, in the context of A po A ‐ I function in contrast to recent models derived by other methods.