Trends Biochem Sci. 2021 Apr 23:S0968-0004(21)00065-7. doi: 10.1016/j.tibs.2021.03.007. Online ahead of print.
Elevator-type transporters are a group of proteins translocating nutrients and metabolites across cell membranes. Despite structural and functional differences, elevator-type transporters use a common mechanism of substrate translocation via reversible movements of a mobile core domain (the elevator), which includes the substrate binding site, along a rigid scaffold domain, stably anchored in the plasma membrane. How substrate specificity is determined in elevator transporters remains elusive. Here, I discuss how a recent report on the sliding elevator mechanism, seen under the context of genetic analysis of a prototype fungal transporter, sheds light on how specificity might be genetically modified. I propose that flexible specificity alterations might occur by ‘loosening’ of the sliding mechanism from tight coupling to substrate binding.