Comparative genomics of bacterial zinc regulons: Enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins
Comparative genomics of bacterial zinc regulons: Enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins
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DOI：
10.1073/pnas.1733691100
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发表时间：
2003-08-19
影响因子：
11.1
通讯作者：
Gelfand, MS
中科院分区：
文献类型：
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作者：
Panina, EM;Mironov, AA;Gelfand, MS
锌是许多蛋白质的重要组成部分，但在高浓度下，它对细胞有毒。因此，它的运输是由锌阻遏物ZUR的变形菌和革兰氏阳性细菌从芽孢杆菌组和AdcR的细菌从链球菌组。比较计算分析使我们能够识别ZUR阻遏物的结合信号GAAATGTTATANTATAACATTTC为γ-变形菌，GTAATGTAATAACATTAC为土壤杆菌组，GATATGTTATAACATATC为红球菌组，TAAATCGTAATNATTACGATTTA为革兰氏阳性菌，和TTAACYRGTTAA的链球菌AdcR阻遏物。除了已知的转运蛋白和它们的旁系同源物，锌调节子被预测含有ATP结合盒的候选组分zinT（大肠杆菌中的B 1995和枯草芽孢杆菌中的yrpE）。在编码来自许多致病性链球菌的肺炎球菌组氨酸三联体（PHT）蛋白的基因上游鉴定了候选AdcR结合位点。该家族的蛋白质功能分析表明，PHT蛋白参与了入侵过程。最后，锌的阻遏预测的基因编码的核糖体蛋白的各种旁系同源物。所有这些蛋白质的原始拷贝都含有锌带基序，因此可能与锌结合，而这些基序在锌调节的旁系同源物中被破坏。我们建议，这些旁系同源物在锌饥饿条件下的诱导导致其掺入核糖体的一部分，而不是原来的核糖体蛋白质，后者然后降解，随后释放一些锌的利用由其他蛋白质。因此，我们预测一种机制，以维持锌的可用性为必需的酶。
Zinc is an important component of many proteins, but in large concentrations it is poisonous to the cell. Thus its transport is regulated by zinc repressors ZUR of proteobacteria and Gram-positive bacteria from the Bacillus group and AdcR of bacteria from the Streptococcus group. Comparative computational analysis allowed us to identify binding signals of ZUR repressors GAAATGTTATANTATAACATTTC for gamma-proteobacteria, GTAATGTAATAACATTAC for the Agrobacterium group, GATATGTTATAACATATC for the Rhododoccus group, TAAATCGTAATNATTACGATTTA for Gram-positive bacteria, and TTAACYRGTTAA of the streptococcal AdcR repressor. In addition to known transporters and their paralogs, zinc regulons were predicted to contain a candidate component of the ATP binding cassette, zinT (b 1995 in Escherichia coli and yrpE in Bacillus subtilis). Candidate AdcR-binding sites were identified upstream of genes encoding pneumococcal histidine triad (PHT) proteins from a number of pathogenic streptococci. Protein functional analysis of this family suggests that PHT proteins are involved in the invasion process. Finally, repression by zinc was predicted for genes encoding a variety of paralogs of ribosomal proteins. The original copies of all these proteins contain zinc-ribbon motifs and thus likely bind zinc, whereas these motifs are destroyed in zinc-regulated paralogs. We suggest that the induction of these paralogs in conditions of zinc starvation leads to their incorporation in a fraction of ribosomes instead of the original ribosomal proteins; the latter are then degraded with subsequent release of some zinc for the utilization by other proteins. Thus we predict a mechanism for maintaining zinc availability for essential enzymes.