Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR.
Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR.
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DOI：
10.1111/j.1365-2958.2009.06616.x
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发表时间：
2009-03
影响因子：
3.6
通讯作者：
Rajagopal L
中科院分区：
文献类型：
--
作者：
Lin WJ;Walthers D;Connelly JE;Burnside K;Jewell KA;Kenney LJ;Rajagopal L
所有活着的有机体都为了生存和生存而与外部环境进行交流。在原核生物中，通讯是通过由组氨酸激酶和反应调节因子组成的双组分系统(TCS)实现的。在真核生物中，信号转导是通过丝氨酸/苏氨酸和酪氨酸激酶完成的。尽管TCS和丝氨酸/苏氨酸激酶在原核生物中共存，但这些家族之间的直接相互作用首先在B群链球菌(GBS)中被描述，丝氨酸/苏氨酸激酶(Stk1)和TCS(COVR/CoVS)共同调节GBS中的毒素表达。通常，像COVR这样的调节子的启动子结合是由保守的活性部位天冬氨酸(D53)的磷酸化控制的。在这项研究中，我们发现Stk1在苏氨酸65处使COVR磷酸化。通过模拟磷酸化和沉默替代来评估COVR在GBS中的苏氨酸磷酸化的功能结果。与编码非磷酸化T65A等位基因的菌株不同，编码仿磷T65E等位基因的GBS缺乏COVR调节。此外，与野生型或T65A COVR相比，T65E COVR不能结合启动子DNA，在D53处磷酸化程度降低，与Stk1磷酸化的COVR相似。总而言之，我们为一种新的反应调节控制机制提供了证据，该机制使GBS(以及可能的其他原核生物)能够微调基因表达以适应环境。
All living organisms communicate with the external environment for their survival and existence. In prokaryotes, communication is achieved by two-component systems (TCS) comprising histidine kinases and response regulators. In eukaryotes, signalling is accomplished by serine/threonine and tyrosine kinases. Although TCS and serine/threonine kinases coexist in prokaryotes, direct cross-talk between these families was first described in Group B Streptococcus (GBS).Aserine/threonine kinase (Stk1) and a TCS (CovR/CovS) co-regulate toxin expression in GBS. Typically, promoter binding of regulators like CovR is controlled by phosphorylation of the conserved active site aspartate (D53). In this study, we show that Stk1 phosphorylates CovR at threonine 65. The functional consequence of threonine phosphorylation of CovR in GBS was evaluated using phosphomimetic and silencing substitutions. GBS encoding the phosphomimetic T65E allele are deficient for CovR regulation unlike strains encoding the non-phosphorylated T65A allele. Further, compared with wild-type or T65A CovR, the T65E CovR is unable to bind promoter DNA and is decreased for phosphorylation at D53, similar to Stk1-phosphorylated CovR. Collectively, we provide evidence for a novel mechanism of response regulator control that enables GBS (and possibly other prokaryotes) to fine-tune gene expression for environmental adaptation.
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影响因子：
3.2
作者：
Gusa, Asiya A.;Gao, Jinxin;Scott, June R.
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影响因子：
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发表时间：
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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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