Oral Presentation 12th Australian Peptide Conference 2017

ABC proteins in peptide transport from bacteria to man  – role in stress, sex and protection against drugs (#34)

Balazs Sarkadi 1
  1. Research Centre Hungarian Acad. Sci, Budapest, Hungary

ATP Binding Cassette (ABC) transporters form a superfamily of membrane proteins, responsible for the translocation of a large variety of substrates, including peptides. ABC exporters, present from bacteria to man, are primary active transporters using the energy of ATP hydrolysis, contain cytoplasmic nucleotide binding domains responsible for ATP binding and hydrolysis, and large membrane-spanning domains, responsible for substrate translocation and specificity. Both in Gram negative and Gram positive bacteria numerous self-protecting and/or rival-killing amphiphilic peptides, including e.g. Nisin, Subtilin, Epidermin, or Mersacidin, as well as peptide pheromones, including Plantaracin A, are exported by selected ABC transporters. Interestingly, in most cases the secretion of these antimicrobial or growth modifying peptides, ensuring both self-immunity and toxicity against the neighbors, are induced in a hostile environment by metabolic or other stress conditions. Among the unicellular eukaryotes, yeasts express a large variety of inducible ABC exporters, involved in the extrusion of endogenous drug-like peptides or mating peptide pheromones, and the protection against antifungal agents. In some plants glutathione and phytochelatin complexes of heavy metals, as well as peptide phytotoxins are actively extruded by ABC transporters, thus providing metal and bacterial toxin resistance. In humans, several ABC multidrug transporters, including ABCB1, ABCCs and ABCG2, are involved in peptide transport. Again, glutathione conjugates of drugs and metals are actively extruded by the ABCC type proteins, hydrophobic peptides are transported with high affinity by ABCB1, while ABCG2 may have a role in amyloid peptide extrusion from the brain. In addition, the protection of our cells against virus invasion is based on viral peptide transport by the endoplasmic reticulum ABC transporters. In this presentation I plan to review the recently established structural and functional features of the ABC exporter proteins, and provide examples for the medical importance of these transporters in developing new antibacterial and anticancer peptides.