engleski

Theoretical model of human apolipoprotein B100 tertiary structure

Low density lipoprotein (LDL) particles are the main cholesterol carriers in human plasma. The organisation of the particle composed of apolar lipids and phospholipid monolayer stabilized by apolipoprotein B100 (apoB), is highly complex and still unknown. ApoB is extremely large protein (4563 amino acids) and very little is known about its structure. A 3D model of the N- terminal region has been recently proposed and has provided interesting insights about the physico-chemical properties of the protein, and putative interaction zones with lipids. In the present paper, we propose the first tentative 3D modelling for most remaining residues. All predicted features emerging from the models are confronted with agreement to experimental data available. Using different up-to-date predictions methods, we decomposed the protein in 8 domains and predicted 3D structure for each of them. The analysis of hydrophobic patches, polar regions, coupled with functional predictions based on the 3D models, gives new clues to understanding of the functional role of apoB. We suggest precise regions putatively involved in the lipids interaction, and discuss the position of apoB at the LDL particle. Finally, we propose relative organization of the domains, providing a shape quite compatible with the low resolution electron microscopy map.

LDL; apoB; homology modeling; threading; lipid-protein interactions

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