title: Modular structure of solubilized human apolipoprotein B-100. Low resolution model revealed by small angle neutron scattering.
abstract: Being intimately involved in cholesterol transport and lipid metabolism human low density lipoprotein (LDL) plays a prominent role in atherogenesis and cardiovascular diseases. The receptor-mediated cellular uptake of LDL is triggered by apolipoprotein B-100 (apoB-100), which represents the single protein moiety of LDL. Due to the size and hydrophobic nature of apoB-100, its structure is not well characterized. Here we present a low resolution structure of solubilized apoB-100. We have used small angle neutron scattering in combination with advanced shape reconstruction algorithms to generate a three-dimensional model of lipid-free apoB-100. Our model clearly reveals that apoB-100 is composed of distinct domains connected by flexible regions. The apoB-100 molecule adopts a curved shape with a central cavity. In comparison to LDL-associated apoB-100, the lipid-free protein is expanded, whereas according to spectroscopic data the secondary structure is widely preserved. Finally, the low resolution model was used as a template to reconstruct a hypothetical domain organization of apoB-100 on LDL, including information derived from a secondary structure prediction.
authors.affiliation: Institute of Biophysics and X-ray Structure Research, Austrian Academy of Sciences, Schmiedlstrasse 6, A-8042 Graz, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Johs
authors.forename: Michal
authors.initials: M
authors.lastname: Hammel
authors.forename: Ines
authors.initials: I
authors.lastname: Waldner
authors.forename: Roland P
authors.initials: RP
authors.lastname: May
authors.forename: Peter
authors.initials: P
authors.lastname: Laggner
authors.forename: Ruth
authors.initials: R
authors.lastname: Prassl
mesh_terms: D000465:Algorithms; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry*; D002942:Circular Dichroism; D003902:Detergents / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D009502:Neutrons; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D013053:Spectrophotometry
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D003902:Detergents; D008055:Lipids