Download MendeleyCrystal structures of a ZIP zinc transporter reveal a binuclear metal center in the transport pathway.
Zhang, T., Liu, J., Fellner, M., Zhang, C., Sui, D., Hu, J.(2017) Sci Adv 3: e1700344-e1700344
- PubMed: 28875161
- DOI: https://doi.org/10.1126/sciadv.1700344
- Primary Citation of Related Structures:
5TSA, 5TSB - PubMed Abstract:
Zrt/Irt-like proteins (ZIPs) play fundamental roles in metal metabolism/homeostasis and are broadly involved in numerous physiological and pathological processes. The lack of high-resolution structure of the ZIPs hinders understanding of the metal transport mechanism. We report two crystal structures of a prokaryotic ZIP in lipidic cubic phase with bound metal substrates (Cd 2+ at 2.7 ? and Zn 2+ at 2.4 ?). The structures revealed a novel 3+2+3TM architecture and an inward-open conformation occluded at the extracellular side. Two metal ions were trapped halfway through the membrane, unexpectedly forming a binuclear metal center. The Zn 2+ -substituted structure suggested asymmetric functions of the two metal-binding sites and also revealed a route for zinc release. Mapping of disease-causing mutations, structure-guided mutagenesis, and cell-based zinc transport assay demonstrated the crucial role of the binuclear metal center for human ZIP4. A metal transport mechanism for the ZIP from Bordetella bronchiseptica was proposed, which is likely applicable to other ZIPs.
Organizational Affiliation:
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
