Structural basis for autoregulation of the zinc transporter YiiP.
Zinc transporters have crucial roles in cellular zinc homeostatic control. The 2.9-A resolution structure of the zinc transporter YiiP from Escherichia coli reveals a richly charged dimer interface stabilized by zinc binding. Site-directed fluorescence 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, where they are well positioned to transmit zinc-induced interdomain 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.
Lu
Min
M
Biology Department, Brookhaven National Laboratory, Upton, New York, USA.
Chai
Jin
J
Fu
Dax
D
D001665:Binding Sites; D020134:Catalytic Domain; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000502:physiology*; D008628:Mercury / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012492:Salts / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D008670:Metals; D012492:Salts; C486459:YiiP protein, E coli; D008628:Mercury; D015032:Zinc