EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde.
EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde.
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DOI：
10.1371/journal.pbio.3001208
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发表时间：
2021-05
期刊：
影响因子：
9.8
通讯作者：
Marx CJ
中科院分区：
文献类型：
--
作者：
Bazurto JV;Nayak DD;Ticak T;Davlieva M;Lee JA;Hellenbrand CN;Lambert LB;Benski OJ;Quates CJ;Johnson JL;Patel JS;Ytreberg FM;Shamoo Y;Marx CJ
正常的细胞过程会产生有毒的代谢物，细胞必须加以缓解。甲醛是一种普遍的应激源和强大的代谢毒素，在从细菌到人类的有机体中产生。甲基营养细菌面临着严峻的挑战，因为它们产生甲醛，作为单碳代谢的专有中心中间体。据推测，几十年来，甲基营养菌中存在着感知和响应甲醛的机制，但从未被发现。在这里，我们发现了DUF336结构域家族的一个成员，命名为EfgA，意思是增强甲醛生长，它在Extorquens PA1的内源甲醛胁迫反应中发挥着重要作用，几乎只在甲基营养类群中发现。我们的实验分析表明，EfgA是一种甲醛传感器，可以在甲醛水平升高时迅速阻止生长。EfgA在大肠杆菌中的异源表达增加了对甲醛的抗性，表明其相互作用伙伴广泛且保守。EfgA代表了第一个不涉及酶解毒的甲醛应激反应系统的例子。因此，EfgA在细菌中包含一种独特的应激反应机制，通过这种机制，单个蛋白质直接感觉到有毒细胞内代谢物水平的升高，并保护细胞免受潜在的损害。已知的甲醛应激反应系统包括酶解毒作用。在这里，作者表明，甲醛传感器EfgA在甲基紫红藻内源甲醛胁迫反应中发挥重要作用，阻止细胞对甲醛水平升高的反应，并且几乎仅在甲基营养类群中发现。
Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M. extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage. The known formaldehyde stress response systems involve enzymatic detoxification. Here, the authors show that the formaldehyde sensor efgA plays an important role in the endogenous formaldehyde stress response in Methylorubrum extorquens, halting cell growth in response to elevated levels of formaldehyde, and is found almost exclusively in methylotrophic taxa.
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影响因子：
4.5
作者：
Bazurto JV;Riazi S;D'Alton S;Deatherage DE;Bruger EL;Barrick JE;Marx CJ
通讯作者：
Marx CJ
开发针对甲甲基甲虫的优化培养基，菌株和高通量培养方法。
影响因子：
3.7
作者：
Delaney NF;Kaczmarek ME;Ward LM;Swanson PK;Lee MC;Marx CJ
通讯作者：
Marx CJ
影响因子：
56.9
作者：
Chistoserdova, L;Vorholt, JA;Lidstrom, ME
通讯作者：
Lidstrom, ME
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC