Modelling of Nef Interaction with ABCA1 Revealed Potential Binding Sites For Inhibitor Compounds

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Anastasia A. Anashkina¹, Yaroslav V. Tkachev², Alexei A. Adzhubei³
¹EIMB RAS, Moscow, Russia, nastya@eimb.ru
²EIMB RAS, Moscow, Russia, yat@eimb.ru
³EIMB RAS, Moscow, Russia, alexei.adzhubei@eimb.ru

The effect of HIV-1 Nef protein on the demyelination of central nervous system cells is mediated by its effect on the cholesterol transporter protein ABCA1. To determine the possible interactions of Nef-ABCA1, an expert model of the cytoplasmic fragment ABCA1 was constructed and modelling of the reciprocal binding sites in the Nef and ABCA1 structures was carried out. This made it possible to determine the interface for the interaction of proteins and localize binding sites in them.

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Nikolay Alemasov

3 years ago

Dear Anastasia, could you, please, clarify what kind of docking was conducted?

Elena Ignatieva

3 years ago

Did I understand correctly that Nef may disrupt lipid metabolism in all cells of the human body, even if only part of them are infected with HIV?
Can you characterize in more details the structure and composition of extracellular vesicles that deliver Nef molecules into cell? Do this vesicles enter the cell via receptor on the cell membrane, or it is unknown?

Nikita Ivanisenko

3 years ago

Dear Anastasia, the generated models of ABCA1-Nef seems to be promising! Have you checked if there is functional polymorphism/mutagenesis data of ABCA1 or Nef proteins that can be used to validate the predicted residues involved in protein-protein interaction? How targetable with small molecules do you consider these sites, i.e. do they have “druggable” properties to fit small molecule ? Can it be targeted with antibodies as an alternative strategy?