Cryo-electron microscopy structures of a high-affinity zinc ABC transporter

How do bacteria acquire scarce Zn²⁺ to fuel vital cellular functions? Microorganisms employ high-affinity Zn²⁺ ABC transporters, yet their structures and regulation are poorly understood. Here, we report cryo-EM structures of the Escherichia coli ZnuB–ZnuC complex, revealing a ZnuB homodimer in an outward-facing, sealed conformation with a central hydrophilic cavity and ZnuC subunits composed of an N-terminal ATP-binding cassette and a C-terminal zinc-sensing domain (ZSD). Zn²⁺ binding to the ZSD locks the transporter in an inhibited state regardless of nucleotide, whereas under low–Zn²⁺ conditions, ZSD C-terminal disorder permits ATP-driven zinc uptake. These findings clarify the molecular basis of Zn²⁺ acquisition and highlight new targets for disrupting metal homeostasis in pathogens.