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The authors show cryo-electron microscopy structures of the human high-affinity sodium–dicarboxylate cotransporter, responsible for dicarboxylate import into the cell, in complex with various substrates and in different states establish the basis of substrate recognition, differentiation and release, as well as regulation of transport domain movement.

A channel for the transport of hydrosulphide ions in Clostridium difficile is identified and shown to be polyspecific, being a member of the formate/nitrite transporter family.

Small transporters pose a challenge for cryo-EM structure elucidation. Here, the authors tackled this limitation by rigidly fusing a fiducial marker to a transporter C-terminus, enabling multiple structures to be elucidated from a single sample.

Efflux pumps confer antibiotic resistance by coupling proton import with drug export. In this work, the authors uncover the proton-coupled transport mechanism for the clinically relevant efflux pump NorA from the pathogenic bacterium S. aureus.

Structures of the human sodium-dependent citrate transporter NaCT in complexes with citrate or a small-molecule inhibitor reveal how the inhibitor—which binds to the same site as citrate—arrests the transport cycle of NaCT.

DASS carboxylate transporters linked to metabolic diseases couple the Na⁺ gradient to nutrient uptake. Here, the authors unravel the structural basis by which Na⁺ binding coordinates substrate interactions, revealing a distinct coupling mechanism.

Cryo-EM analysis of the quinolone transporter NorA in complex with synthetic antigen-binding fragments (Fabs) inspired peptide mimics of the Fabs that inhibit methicillin-resistant Staphylococcus aureus in combination with the antibiotic norfloxacin.

Membrane transporter proteins switch between conformational states to move substrates across membranes. The transition between these states can now be studied using single-molecule experiments.

Bacterial energy-coupling factor (ECF) transporters mediate ATP-dependent uptake of essential environmental micronutrients. Biochemical and fluorescence analyses now show that ATP binding promotes release of a substrate-capturing subunit that dynamically reassociates with the transmembrane module during the transport cycle.

Sertraline (Zoloft) and fluoxetine (Prozac) are selective serotonin-reuptake inhibitors (SSRIs) that are widely prescribed to treat depression. They bind to the presynaptic plasma membrane serotonin transporter (SERT) and inhibit serotonin uptake. Both these drugs possess halogen atoms, but the structural basis for the specificity of SERT for these inhibitors was not known. Zhou et al. now report the crystal structure of LeuT, a bacterial SERT homolog in complex with three different SSRIs. The halogen atoms of all three bind within exactly the same pocket of LeuT, and mutations within this pocket in SERT markedly reduce the transporter's affinity for SSRIs but not for tricyclic antidepressants.

The structure of the formate channel FocA from Vibrio cholerae reveals a pentamer, with each monomer possessing its own substrate translocation pore. The selectivity filter consists of a central constriction ring and a cytoplasmic slit, which binds two formate ions. Surprisingly, FocA shares many similarities with aquaporin and glycerol channels.

The cytosolic concentration of citrate partially depends on its direct import across the plasma membrane by the Na⁺-dependent citrate transporter (NaCT); here the X-ray crystal structure of a bacterial homologue of NaCT is reported, which, along with transport-activity studies, suggests how specific conformational changes facilitate substrate translocation across the cellular membrane.