Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter.

Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter.
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DOI:
10.1038/s41467-023-36048-4
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发表时间:
2023-01-24
影响因子:
16.6
通讯作者:
Hu, Jian
Hu, Jian
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhang, Yao;Jiang, Yuhan;Gao, Kaifu;Sui, Dexin;Yu, Peixuan;Su, Min;Wei, Guo-Wei;Hu, Jian

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Zrt-/ irt样蛋白(ZIP)家族由普遍表达的二价金属转运蛋白组成,在维持锌、铁和锰的系统和细胞稳态中起关键作用。本文采用结构生物学、进化协方差、计算建模和多种生化分析相结合的方法,对一株原核细菌细菌(Bordetella bronchiseptica, BbZIP)进行了研究,以解决ZIP家族尚未确定的转运机制问题。向内构象的载脂蛋白状态结构揭示了一个拆卸的运输位点,改变了螺旋间的相互作用,重要的是,相对于其他TM, 4-跨膜螺旋束(TM)的刚体运动。计算生成和生化验证的面向外的构象模型显示,携带转运位点的4-TM束向细胞外侧滑动约8 Å,反对介导二聚化的静态tm。这些发现使我们得出结论,BbZIP是一种电梯式运输机。ZIP家族(SLC39A)参与过渡金属稳态。在这里,作者使用综合方法得出结论,支气管杆菌的ZIP (BbZIP)利用电梯式运输机制实现交替进入。
The Zrt-/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent metal transporters critically involved in maintaining systemic and cellular homeostasis of zinc, iron, and manganese. Here, we present a study on a prokaryotic ZIP from Bordetella bronchiseptica (BbZIP) by combining structural biology, evolutionary covariance, computational modeling, and a variety of biochemical assays to tackle the issue of the transport mechanism which has not been established for the ZIP family. The apo state structure in an inward-facing conformation revealed a disassembled transport site, altered inter-helical interactions, and importantly, a rigid body movement of a 4-transmembrane helix (TM) bundle relative to the other TMs. The computationally generated and biochemically validated outward-facing conformation model revealed a slide of the 4-TM bundle, which carries the transport site(s), by approximately 8 Å toward the extracellular side against the static TMs which mediate dimerization. These findings allow us to conclude that BbZIP is an elevator-type transporter. The ZIP family (SLC39A) is involved in transition metal homeostasis. Here, authors use integrated approaches to conclude that the ZIP from Bordetella bronchiseptica (BbZIP) utilizes the elevator-type transport mechanism to achieve alternating access.
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