Structural features and dynamics properties of human apolipoprotein A-I in a model of synthetic HDL
| Autor: | Cesare R. Sirtori, Guido Franceschini, Elisabetta Gianazza, Ivano Eberini, Laura Calabresi, Alessandro Guerini Rocco, Cristina Sensi |
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| Rok vydání: | 2009 |
| Předmět: |
Molecular model
Apolipoprotein B Molecular Dynamics Simulation Protein Structure Secondary Molecular dynamics chemistry.chemical_compound Amphiphile Materials Chemistry Humans Physical and Theoretical Chemistry Protein secondary structure Spectroscopy biology Apolipoprotein A-I Chemistry Cholesterol nutritional and metabolic diseases Computer Graphics and Computer-Aided Design Protein tertiary structure Biochemistry Models Chemical biology.protein Thermodynamics lipids (amino acids peptides and proteins) Biological system Lipoproteins HDL Lipoprotein |
| Zdroj: | Journal of molecular graphicsmodelling. 28(4) |
| ISSN: | 1873-4243 |
| Popis: | High-density lipoproteins (HDL) play a major role in the reverse transport of cholesterol and have antiatherogenic activities. Their major protein component is apolipoprotein (apo) A-I. While apoA-I amphipathic α-helix based secondary structure has been extensively investigated, for its lipid-bound tertiary structure only theoretical models have been proposed. In the past years, experimental approaches aimed at a direct visualization of HDL structure have been exploited, but data obtained through different microscopy techniques are conflicting and do not settle the issue. Here we present a 50 ns molecular dynamics simulation of a synthetic HDL containing two molecules of apoA-I and 101 of l -α-palmitoyl-oleoyl-phosphatidylcholine. Essential dynamics and structural property investigations suggest that the stabilization of the system is obtained through specific motions, whose driving forces are protein–phospholipid interactions. The most important are: the relative sliding of the two apoA-I molecules along their major axes, the relative rotation of the protein chains, and the out-of-plane deformation around proline hinges. The sliding and the out-of-plane deformation allow apoA-I to optimize its interactions with phospholipids, while the rotation is useful to maximize protein–protein salt bridges. The correspondence between computed parameters and their experimental counterparts contributes to validate our model and its dynamic behaviors. Our findings help in defining a molecular model for apoA-I contained in HDL and suggest a possible mechanism through which apoA-I can vary its diameter and accommodate different numbers of phospholipids during the metabolism of HDL. |
| Databáze: | OpenAIRE |
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