Eterodimero apoA-IM-apoA-II: proposta di un modello strutturale a supporto della sua particolare sensibilità alla proteolisi


Abstract


In this study, we propose a structure for the heterodimer between
apolipoprotein A-IMilano and apolipoprotein A-II (apoA-IM–apoA-II) in
a synthetic high-density lipoprotein (HDL) containing L--palmitoyloleoyl
phosphatidylcholine. We applied bioinformatics/computational tools and
procedures, such as molecular docking, molecular and essential dynamics,
starting from published crystal structures for apolipoprotein A-I and
apolipoprotein A-II. Structural and energetic analyses onto the simulated
system showed that the molecular dynamics produced a stabilized synthetic
HDL. The essential dynamic analysis showed a deviation from the starting
belt structure. Our structural results were validated by limited proteolysis
experiments on HDL from apoA-IM carriers in comparison with control HDL.
The high sensitivity of apoA-IM–apoA-II to proteases was in agreement with
the high root mean-square fluctuation values and the reduction in secondary
structure content from molecular dynamics data. Circular dichroism on
synthetic HDL containing apoA-IM–apoA-II was consistent with the -helix
content computed on the proposed model.

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