Identification of a novel tetrameric structure for human apolipoprotein-D

Publication date: Available online 6 June 2018Source: Journal of Structural BiologyAuthor(s): Claudia S. Kielkopf, Jason K.K. Low, Yee-Foong Mok, Surabhi Bhatia, Tony Palasovski, Aaron J. Oakley, Andrew E. Whitten, Brett Garner, Simon H.J. BrownAbstractApolipoprotein-D is a 25 kDa glycosylated member of the lipocalin family that folds into an eight-stranded β-barrel with a single adjacent α-helix. Apolipoprotein-D specifically binds a range of small hydrophobic ligands such as progesterone and arachidonic acid and has an antioxidant function that is in part due to the reduction of peroxidised lipids by methionine-93. Therefore, apolipoprotein-D plays multiple roles throughout the body and is protective in Alzheimer’s disease, where apolipoprotein-D overexpression reduces the amyloid-β burden in Alzheimer’s disease mouse models.Oligomerisation is a common feature of lipocalins that can influence ligand binding. The native structure of apolipoprotein-D, however, has not been conclusively defined. Apolipoprotein-D is generally described as a monomeric protein, although it dimerises when reducing peroxidised lipids.Here, we investigated the native structure of apolipoprotein-D derived from plasma, breast cyst fluid (BCF) and cerebrospinal fluid. In plasma and cerebrospinal fluid, apolipoprotein-D was present in high-molecular weight complexes, potentially in association with lipoproteins. In contrast, apolipoprotein-D in BCF formed distinct oligomeric species. We assesse...
Source: Journal of Structural Biology - Category: Biology Source Type: research