title: [Molecular mechanism of AB5 toxin A-subunit translocation into the target cells].
abstract: AB5 toxins are pore-forming protein complexes, which destroy eukaryotic target cells inactivating essential enzyme complexes through protein ADP-ribosylation or glycosylation by enzymatically active A1 subunits. The B-subunit pentamer interacts with the target cell receptor, induces membrane pore formation, and initiates receptor-mediated endocytosis. In the present article, we propose a model of A1-subunit translocation in the form of a globular structure, as opposed to the generally accepted hypothesis of A-subunit unfolding in the acidic milieu of the endosome followed by its transport in the form of unfolded polypeptide and refolding in the cytoplasm. This model is based on physical-chemical processes and explains why an endosome, but not an exosome, is formed. A-subunit translocation into the cytosol is driven by the proton potential difference generated by K/Na- and H(+)-ATPases. After reduction of the disulphide bond between A1 and A2 fragments by intracellular enzymes, B-subunit returns back into the endosome, where they are destroyed by endosomal proteases, and the pore is closed. Endosome integrates into the cellular membrane, and membrane-bound enzymatic complexes (ATPases and others) return back to their initial position. The proposed model of receptor-mediated endocytosis is a universal molecular mechanism of translocation of effector toxin molecule subunits or any other proteins into the target cell, as well as of cell membrane reparation after any cell membrane injury by pore-forming complexes.
authors.forename: A N
authors.initials: AN
authors.lastname: Noskov
mesh_terms: D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry; D055598:Chemical Phenomena; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D011992:Endosomes / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D021381:Protein Transport; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D021122:Protein Subunits; D006180:Proton-Translocating ATPases; D000254:Sodium-Potassium-Exchanging ATPase