Crystal structures of a ZIP zinc transporter reveal a binuclear metal center in the transport pathway.
Crystal structures of a ZIP zinc transporter reveal a binuclear metal center in the transport pathway.
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拉链锌转运蛋白的晶体结构在传输途径中揭示了双核金属中心。
DOI：
10.1126/sciadv.1700344
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发表时间：
2017-08
期刊：
影响因子：
13.6
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Zhang T;Liu J;Fellner M;Zhang C;Sui D;Hu J
ZIP锌转运蛋白的结构揭示了在转运途径中具有双核金属中心的向内开放构象。Zrt/Irt-like蛋白（ZIPs）在金属代谢/稳态中起着重要作用，广泛参与许多生理和病理过程。高分辨率的ZIPs结构的缺乏阻碍了对金属输运机制的理解。我们报道了两种原核ZIP的晶体结构，其在具有结合的金属底物（Cd 2+在2.7 μ mol/L和Zn 2+在2.4 μ mol/L）的无规立方相中。该结构揭示了一种新的3+2+ 3 TM结构和在细胞外侧封闭的向内开放的构象。两个金属离子被困在膜的一半，意外地形成了一个双核金属中心。Zn 2+取代的结构表明两个金属结合位点的不对称功能，也揭示了锌释放的途径。致病突变的定位，结构指导的诱变和基于细胞的锌转运测定证明了人类ZIP 4双核金属中心的关键作用。提出了支气管败血波氏杆菌ZIP的金属转运机制，该机制可能适用于其他ZIP。
Structures of a ZIP zinc transporter reveal an inward-open conformation with a binuclear metal center in the transport pathway. 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 (Cd2+ at 2.7 Å and Zn2+ 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 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.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
10.6
作者：
Jeong, Jeeyon;Eide, David J.
通讯作者：
Eide, David J.
影响因子：
64.8
作者：
Bai Y;McCoy JG;Levin EJ;Sobrado P;Rajashankar KR;Fox BG;Zhou M
通讯作者：
Zhou M
DOI：
10.1073/pnas.0709307104
发表时间：
2007-11-20
影响因子：
11.1
作者：
Li, Min;Zhang, Yuqing;Yao, Qizhi
通讯作者：
Yao, Qizhi
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH