Zinc TransporterYiiPfromEscherichia coli

Abstract

YiiP from Escherichia coli belongs to the protein family of cation diffusion facilitator (CDF). CDFs play critical roles in metal homeostatic controls in microbes, plants, and mammals. They utilize the proton motive force to drive effluxes of transition metal ions out of the cytoplasm. Bacterial CDFs primarily contribute to metal resistance while mammalian CDFs are more involved in metal metabolism and cellular signaling. The crystal structure of YiiP reveals a Y‐shaped dimeric architecture, consisting of a transmembrane domain and a cytoplasmic domain that adopts a metallochaperone‐like fold. The molecular details of three distinct zinc coordination sites in YiiP delineate how metallochemistry is tailored to three central functions of CDFs: selective metal binding, rapid transport kinetics, and allosteric regulation of the transport activity. An integration of the structural information and existing biochemical data allows us to propose a two‐modular model for the operation of YiiP. In this model, the transmembrane domain is responsible for a stoichiometric zinc‐for‐proton exchange across the membrane barrier. The cytoplasmic domain detects the fluctuation of zinc concentrations and responds with a conformational change that is transmitted to regulate the activity of the transmembrane domain. In addition, the cytoplasmic domain may also serve as a zinc receiving module for uploading of the zinc cargo from a putative zinc‐metallochaperone.