Hydrogen peroxide inactivates the Escherichia coli Isc iron-sulphur assembly system, and OxyR induces the Suf system to compensate.
Hydrogen peroxide inactivates the Escherichia coli Isc iron-sulphur assembly system, and OxyR induces the Suf system to compensate.
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DOI：
10.1111/j.1365-2958.2010.07418.x
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发表时间：
2010-12
影响因子：
3.6
通讯作者：
Imlay JA
中科院分区：
文献类型：
--
作者：
Jang S;Imlay JA
环境中的H2 O2会对大肠杆菌造成多种伤害，包括脱水酶[4 Fe-4S]簇氧化转化为无活性的[3 Fe-4S]形式。H2 O2胁迫的E. coli激活OxyR调节子。该调节子包括suf操纵子，其编码管家Isc铁硫簇组装系统的替代方案。以前研究的[3Fe-4S]簇通过Isc/Suf独立途径修复，因此Suf诱导的基本原理并不明显。使用不能抑制H2 O2的菌株，我们施加慢性低度胁迫，发现suf突变体不能维持异丙基苹果酸异构酶（一种关键的铁硫异构酶）的活性。实验表明，其受损的簇在体内降解超过[3Fe-4S]状态，推测为脱辅基蛋白形式，因此需要从头组装系统来重新激活。令人惊讶的是，亚微摩尔H2 O2中毒的Isc机制，从而创造了一个需要Suf既修复异构酶，并激活新生的Fe-S酶一般。Isc系统的IscS和IscA组分是H2 O2抗性的，这表明氧化剂通过在IscU支架上组装或从IscU支架转移时氧化簇来破坏Isc。与这些结果一致，生物体通常暴露于氧化剂依赖于Suf而不是Isc的集群组装。
Environmental H2O2 creates several injuries in Escherichia coli, including the oxidative conversion of dehydratase [4Fe-4S] clusters to an inactive [3Fe-4S] form. To protect itself, H2O2-stressed E. coli activates the OxyR regulon. This regulon includes the suf operon, which encodes an alternative to the housekeeping Isc iron-sulfur-cluster assembly system. Previously studied [3Fe-4S] clusters are repaired by an Isc/Suf-independent pathway, so the rationale for Suf induction was not obvious. Using strains that cannot scavenge H2O2, we imposed chronic low-grade stress and found that suf mutants could not maintain the activity of isopropylmalate isomerase, a key iron-sulfur dehydratase. Experiments showed that its damaged cluster was degraded in vivo beyond the [3Fe-4S] state, presumably to an apoprotein form, and thus required a de novo assembly system for reactivation. Surprisingly, sub-micromolar H2O2 poisoned the Isc machinery, thereby creating a requirement for Suf both to repair the isomerase and to activate nascent Fe-S enzymes in general. The IscS and IscA components of the Isc system are H2O2-resistant, suggesting that oxidants disrupt Isc by oxidizing clusters as they are assembled on or transferred from the IscU scaffold. Consistent with these results, organisms that are routinely exposed to oxidants rely upon Suf rather than Isc for cluster assembly.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
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影响因子：
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影响因子：
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作者：
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影响因子：
3.2
作者：
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通讯作者：
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