Exploring transporters within the small multidrug resistance family using solid-state NMR spectroscopy

Small multidrug resistance (SMR) proteins comprise a family of bacterial secondary active transporters that confer drug resistance to antiseptics and antibiotics. EmrE has emerged as the model protein of the SMR family and an archetype to understand the ion-coupled transport mechanism. The importance of EmrE is further underscored by its proposed role as an evolutionary predecessor to larger transporters, which stems from the similarity of the antiparallel and asymmetric structure of the EmrE dimer with the inverted repeat fold of efflux pumps within other transport families such as the major facilitator superfamily. This review describes progress to reveal the atomic-scale structure and dynamics of SMR proteins determined under native-like conditions in lipid bilayers using solid-state NMR spectroscopy. The combination of MAS and oriented solid-state NMR approaches developed to study the SMR family serves as a framework for future efforts to uncover structural details of other secondary active transporters that are abundant in biology.