Structural basis for autoregulation of the zinc transporter YiiP

Abstract

Zinc transporters play critical roles in cellular zinc homeostatic control. The 2.9-Å resolution structure of the zinc transporter YiiP from Escherichia coli reveals a richly charged dimer-interface stabilized by zinc binding. Site-directed fluorescent resonance energy transfer (FRET) measurements and mutation-activity analysis suggest that zinc binding triggers hinge movements of two electrically repulsive cytoplasmic domains pivoting around four salt-bridges situated at the juncture of the cytoplasmic and transmembrane domains. These highly conserved salt-bridges interlock transmembrane helices at the dimer-interface, well positioned to transmit zinc-induced inter-domain movements to reorient transmembrane helices, thereby modulating coordination geometry of the active-site for zinc transport. The cytoplasmic domain of YiiP is a structural mimic of metal trafficking proteins and the metal-binding domains of metal-transporting P-type ATPases. The use of this common structural module to regulate metal coordination chemistry may enable a tunable transport activity in response to cytoplasmic metal fluctuations.