ABC transporters: one, two or four extracytoplasmic substrate‐binding sites?

Abstract

Two families of ATP‐binding cassette (ABC) transporters in which one or two extracytoplasmic substrate‐binding domains are fused to either the N‐ or C‐terminus of the translocator protein have been detected. This suggests that two, or even four, substrate‐binding sites may function in the ABC transporter complex. This domain organization in ABC transporters, widely represented among microorganisms, raises new possibilities for how the substrate‐binding protein(s) (SBPs) might interact with the translocator. One appealing hypothesis is that multiple substrate‐binding sites in proximity to the entry site of the translocation pore enhance the transport capacity. We also discuss the implications of multiple substrate‐binding sites in close proximity to the translocator in terms of broadened substrate specificity and possible cooperative interactions between SBPs and the translocator.