Structure and Function of the Zinc Binding Protein ZrgA from Vibrio cholerae.
Structure and Function of the Zinc Binding Protein ZrgA from Vibrio cholerae.
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DOI：
10.3390/ijms24010548
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发表时间：
2022-12-29
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
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ATP结合盒（ABC）转运蛋白是细菌从环境中获取微量元素的主要途径。它们依赖于溶质结合蛋白（SBPs）结合相关底物并将其递送至完整的膜透性酶，以供ATP动力输入细胞质。已知簇A-I的SBPs促进必需金属锌、锰和铁的运输，并且许多SBPs迄今已被表征。一组被称为锌调节基因（zrg）的ABC转运操纵子最近已被证明与假定的SBP（zrgA）一起转运锌，该SBP与经典的簇A-I家族没有同源性，并且最近来自铜绿假单胞菌的代表性蛋白质的晶体结构显示与经典的SBP没有结构相似性。因此，ZrgA蛋白似乎代表了一个新发现的家族，广泛存在于革兰氏阴性细菌，包括人类病原体中的锌SBPs。在这里，我们已经确定了从霍乱弧菌ZrgA的晶体结构，其特点是锌结合在体外和功能在体内。我们还评估了富含组氨酸的序列的作用，该序列似乎是在霍乱弧菌ZrgA中特别长的ZrgA蛋白的标志。结果表明，zrgA基因是关键的操纵子的功能，在这个系统中作为SBP的功能一致。此外，富含His的区域对ZrgA的功能不是必需的，但它确实在体外提供了额外的锌结合位点。ZrgA的结构和锌结合数据揭示了它与铜绿假单胞菌同源物之间有趣的差异，说明了这个很少研究的蛋白质家族的多样性。
ATP binding cassette (ABC) transporters are the primary means by which bacteria acquire trace elements from the environment. They rely on solute binding proteins (SBPs) to bind the relevant substrate and deliver it to the integral membrane permease for ATP-powered import into the cytoplasm. SBPs of cluster A-I are known to facilitate the transport of essential metals zinc, manganese, and iron, and many have been characterized to date. A group of ABC transporter operons dubbed zinc-regulated genes (zrg) have recently been shown to transport zinc with putative SBPs (zrgA) bearing no homology to the classical cluster A-I family, and a recent crystal structure of a representative protein from Pseudomonas aeruginosa shows no structural similarity to classical SBPs. Thus, the ZrgA proteins appear to represent a newly discovered family of zinc SBPs widespread among Gram-negative bacteria, including human pathogens. Here, we have determined the crystal structure of ZrgA from Vibrio cholerae and characterized its zinc binding in vitro and function in vivo. We also assessed the role of a histidine-rich sequence that appears to be a hallmark of ZrgA proteins that is particularly long in V. cholerae ZrgA. The results show that the zrgA gene is critical to the function of the operon, consistent with a function as an SBP in this system. Further, the His-rich region is not essential to the function of ZrgA, but it does provide additional zinc binding sites in vitro. The structure and zinc binding data for ZrgA reveal interesting differences between it and its homologue from P. aeruginosa, illustrating diversity within this little-studied protein family.
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影响因子：
4.8
作者：
Handali, Melody;Roychowdhury, Hridindu;Yukl, Erik T.
通讯作者：
Yukl, Erik T.
影响因子：
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作者：
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DOI：
10.1107/s0907444904019158
发表时间：
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影响因子：
2.2
作者：
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通讯作者：
Cowtan, K
DOI：
10.1107/s2059798321009608
发表时间：
2021-11-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
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作者：
Fiorillo A;Battistoni A;Ammendola S;Secli V;Rinaldo S;Cutruzzolà F;Demitri N;Ilari A
通讯作者：
Ilari A
影响因子：
3
作者：
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通讯作者：
DeTitta, GT