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Structural basis for autoregulation of the zinc transporter YiiP

Nature Structural & Molecular Biology volume 16, pages 1063–1067 (2009)Cite this article

Abstract

Zinc transporters have crucial 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 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.

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Figure 1: YiiP structure and helix packing in the TMD.
Figure 2: Zinc-binding sites.
Figure 3: Electrostatic surface potentials and a model for autoregulation.
Figure 4: Functional characterization.

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Acknowledgements

We thank the staff at beamline X25 of National Synchrotron Light Source of Brookhaven Nation Laboratory for technical assistance during data collection. We also thank J. Shanklin, P. Freimuth, B.P. Rosen, C. Anderson, C. Correll, R. Kaplan and D. Mueller for critically reading the manuscript. This work was supported by the US National Institutes of Health (to D.F.), the US Office of Basic Energy Sciences, Department of Energy (to D.F.) and the Biology Department of Brookhaven National Laboratory.

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  1. Biology Department, Brookhaven National Laboratory, Upton, New York, USA

    Min Lu, Jin Chai & Dax Fu

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Correspondence to Dax Fu.

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Lu, M., Chai, J. & Fu, D. Structural basis for autoregulation of the zinc transporter YiiP. Nat Struct Mol Biol 16, 1063–1067 (2009). https://doi.org/10.1038/nsmb.1662

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