Title

Small angle X-ray scattering analysis of ligand-bound forms of tetrameric apolipoprotein-D

Publication Name

Bioscience Reports

Abstract

Human apolipoprotein-D (apoD) is a glycosylated lipocalin that plays a protective role in Alzheimer's disease due to its antioxidant function. Native apoD from human body fluids forms oligomers, predominantly a stable tetramer. As a lipocalin, apoD binds and transports small hydrophobic molecules such as progesterone, palmitic acid and sphingomyelin. Oligomerisation is a common trait in the lipocalin family and is affected by ligand binding in other lipocalins. The crystal structure of monomeric apoD shows no major changes upon progesterone binding. Here, we used small-angle X-ray scattering (SAXS) to investigate the influence of ligand binding and oxidation on apoD oligomerisation and conformation. As a solution-based technique, SAXS is well suited to detect changes in oligomeric state and conformation in response to ligand binding. Our results show no change in oligomeric state of apoD and no major conformational changes or subunit rearrangements in response to binding of ligands or protein oxidation. This highlights the highly stable structure of the native apoD tetramer under various physiologically relevant experimental conditions.

Open Access Status

This publication may be available as open access

Volume

41

Issue

1

Article Number

BSR20201423

Funding Number

1109831

Funding Sponsor

National Health and Medical Research Council

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Link to publisher version (DOI)

http://dx.doi.org/10.1042/BSR20201423