ABC importers present in prokaryotes, and some plants, transport solutes from the extracellular space into the cytosol.
Consider a typical ABC importer present in Gram-negative bacteria.
The solute first enters the periplasmic space through porins present on the outer membrane. Here, a substrate-binding protein or SBP selectively binds to the solute and carries it to the ABC importer.
Interaction with the SBP brings the two ATPase domains of the importer closer and allows them to bind two ATP molecules and dimerize.
The SBP then releases the solute into the binding site present between the transmembrane domains of the transporter.
ATP hydrolysis changes the conformation of the transporter, releasing the solute into the cytosol.
However, Gram-positive bacteria lack the outer membrane, and the SBP is often a lipoprotein anchored to the cell membrane.
As the solute enters the thick peptidoglycan layer, the SBP binds and brings it closer to the ABC importer.
Upon release from the SBP, the solute is imported into the cell following the same mechanism as Gram-negative bacteria.
ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
Additionally, for the substrate to bind and be translocated, the bacterial importers have substrate-binding proteins (SBP). In gram-negative bacteria, a high-affinity periplasmic SBP typically delivers the solute to the importer present in the inner membrane that pumps it into the cytosol. However, gram-positive bacteria lack the periplasm; hence their binding protein is often a lipid-anchored external SBP, while some also have the binding proteins fused to the transmembrane domain of the transporter itself.
ABC importers are absent in mammals which increases the promise of these importers as therapeutic targets. For example, Mycobacterium tuberculosis, which causes tuberculosis, remains a significant health concern owing to its high mortality rates worldwide. It imports substrates to meet the requirement of nutrient uptake, maintenance of cell integrity, communication, and pathogenicity. Therefore, targeting its importers with antimicrobialsthat mimic transporter substrates, could be a potential drug treatment option.