Function, Structure, and Transport Aspects of ZIP and ZnT Zinc Transporters in Immune Cells.
Function, Structure, and Transport Aspects of ZIP and ZnT Zinc Transporters in Immune Cells.
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DOI：
10.1155/2018/9365747
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发表时间：
2018
影响因子：
4.1
通讯作者：
Kim ST
中科院分区：
文献类型：
--
作者：
Bin BH;Seo J;Kim ST
锌是免疫系统中重要的微量金属，锌转运蛋白参与多种免疫应答。最近的进展揭示了锌跨细胞膜转运的结构和生化基础，其临床意义在于调节免疫细胞如树突状细胞、T细胞、B细胞和肥大细胞中的锌稳态。在这篇综述中，我们讨论了两个主要的哺乳动物锌转运蛋白类型，进口商和出口商的功能，结构和运输方面。首先，Zrt-/Irt样蛋白（ZIPs）介导锌从细胞外或腔侧流入细胞质。人类有14个ZIP家族成员。它们形成具有8个跨膜结构域和各种长度的胞外/胞内结构域的同源或异源二聚体。几个ZIP成员显示出由两个亚结构域组成的特异性胞外结构域，一个富含螺旋的结构域和一个含有脯氨酸-丙氨酸-亮氨酸（PAL）基序的结构域。第二，锌转运蛋白（ZnT）最初是在锌生物学的早期研究中发现的;它介导锌流出，作为锌稳态中ZIPs的对应物。已确定10名家庭成员。它们显示出独特的结构，其特征在于Y形构象和大的胞质结构域。结合小鼠实验对ZIP和ZnT的结构和转运机制的精确、全面的理解将提供有希望的药物靶点，并为鉴定具有治疗潜力的其他转运蛋白奠定基础。
Zinc is an important trace metal in immune systems, and zinc transporters are involved in many immune responses. Recent advances have revealed the structural and biochemical bases for zinc transport across the cell membrane, with clinical implications for the regulation of zinc homeostasis in immune cells like dendritic cells, T cells, B cells, and mast cells. In this review, we discuss the function, structure, and transport aspects of two major mammalian zinc transporter types, importers and exporters. First, Zrt-/Irt-like proteins (ZIPs) mediate the zinc influx from the extracellular or luminal side into the cytoplasm. There are 14 ZIP family members in humans. They form a homo- or heterodimer with 8 transmembrane domains and extra-/intracellular domains of various lengths. Several ZIP members show specific extracellular domains composed of two subdomains, a helix-rich domain and proline-alanine-leucine (PAL) motif-containing domain. Second, ZnT (zinc transporter) was initially identified in early studies of zinc biology; it mediates zinc efflux as a counterpart of ZIPs in zinc homeostasis. Ten family members have been identified. They show a unique architecture characterized by a Y-shaped conformation and a large cytoplasmic domain. A precise, comprehensive understanding of the structures and transport mechanisms of ZIP and ZnT in combination with mice experiments would provide promising drug targets as well as a basis for identifying other transporters with therapeutic potential.
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影响因子：
5.6
作者：
Kimura T;Kambe T
通讯作者：
Kambe T
DOI：
10.1152/ajpendo.1997.272.6.e1002
发表时间：
1997-06-01
影响因子：
5.1
作者：
Beck, FWJ;Prasad, AS;Brewer, GJ
通讯作者：
Brewer, GJ
影响因子：
2.9
作者：
Lamb, AL;Wernimont, AK;Rosenzweig, AC
通讯作者：
Rosenzweig, AC
影响因子：
11.1
作者：
Bin BH;Hojyo S;Hosaka T;Bhin J;Kano H;Miyai T;Ikeda M;Kimura-Someya T;Shirouzu M;Cho EG;Fukue K;Kambe T;Ohashi W;Kim KH;Seo J;Choi DH;Nam YJ;Hwang D;Fukunaka A;Fujitani Y;Yokoyama S;Superti-Furga A;Ikegawa S;Lee TR;Fukada T
通讯作者：
Fukada T
影响因子：
8.2
作者：
Kawasaki, E.;Uga, M.;Eguchi, K.
通讯作者：
Eguchi, K.