5TSB

Crystal structure of the Zrt-/Irt-like protein from Bordetella bronchiseptica with bound Cd2+

Summary for 5TSB

• Entry DOI: 10.2210/pdb5tsb/pdb
• Descriptor: Membrane protein, CADMIUM ION (3 entities in total)
• Functional Keywords: zip, transporter, zinc, cadmium, lipidic cubic phase, binuclear metal center, membrane protein, metal binding protein
• Biological source: Bordetella bronchiseptica (strain ATCC BAA-588 / NCTC 13252 / RB50)
• Total number of polymer chains: 1
• Total formula weight: 32068.56

Authors

Zhang, T.,Fellner, M.,Sui, D.,Liu, J.,Hu, J. (deposition date: 2016-10-28, release date: 2017-09-20, Last modification date: 2024-10-16)

Primary citation

Zhang, T.,Liu, J.,Fellner, M.,Zhang, C.,Sui, D.,Hu, J.
Crystal structures of a ZIP zinc transporter reveal a binuclear metal center in the transport pathway.
Sci Adv, 3:e1700344-e1700344, 2017

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 at 2.7 Å and Zn at 2.4 Å). 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-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 was proposed, which is likely applicable to other ZIPs.

PubMed: 28875161
DOI: 10.1126/sciadv.1700344

Experimental method

X-RAY DIFFRACTION (2.7 Å)