5tsb
Crystal structure of the Zrt-/Irt-like protein from Bordetella bronchiseptica with bound Cd2+
Structural highlights
FunctionZIP_BORBR Selective electrodiffusional channel that mediates the uptake of Zn(2+). Exploits in vivo zinc concentration gradients (maintained by cellular zinc homeostasis) to passively move zinc ions into the cytoplasm. ZIPB-mediated zinc flux is dependent upon pH, but independent of the proton motive force. Is also able to import Cd(2+), but is not permeable to Co(2+), Cu(2+), Fe(2+), Mn(2+) and Ni(2+).[1] Publication Abstract from PubMedZrt/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 (Cd2+ at 2.7 A and Zn2+ at 2.4 A). 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 Zn2+-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. Crystal 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 Sci Adv. 2017 Aug 25;3(8):e1700344. doi: 10.1126/sciadv.1700344. eCollection 2017, Aug. PMID:28875161[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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