Regulatory control of the Streptococcus mutans HdrRM LytTR Regulatory System functions via a membrane sequestration mechanism.,Molecular Microbiology

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Regulatory control of the Streptococcus mutans HdrRM LytTR Regulatory System functions via a membrane sequestration mechanism.
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-07-24 , DOI: 10.1111/mmi.14576
Zhoujie Xie ₁ , Zhengzhong Zou ₂ , Assaf Raz ₃ , Hua Qin ₂ , Vincent Fischetti ₃ , Shan Zhang ₂ , Jens Kreth ₂ , Justin Merritt _{2,

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Affiliation

Bacteria sense and respond to environmental changes via several broad categories of sensory signal transduction systems. Recently, we described the key features of a previously unrecognized, but widely conserved class of prokaryotic sensory system that we refer to as the LytTR Regulatory System (LRS). Our previous studies suggest that most, if not all, prokaryotic LRS membrane proteins serve as inhibitors of their cognate transcription regulators, but the inhibitory mechanisms employed have thus far remained a mystery. Using the Streptococcus mutans HdrRM LRS as a model, we demonstrate how the LRS membrane protein HdrM inhibits its cognate transcription regulator HdrR by tightly sequestering HdrR in a membrane‐localized heteromeric HdrR/M complex. Membrane sequestration of HdrR prevents the positive feedback autoregulatory function of HdrR, thereby maintaining a low basal expression of the hdrRM operon. However, this mechanism can be antagonized by ectopically expressing a competitive inhibitor mutant form of HdrR that lacks its DNA binding ability while still retaining its HdrM interaction. Our results indicate that sequestration of HdrR is likely to be the only mechanism required to inhibit its transcription regulator function, suggesting that endogenous activation of the HdrRM LRS is probably achieved through a modulation of the HdrR/M interaction.

中文翻译：

变形链球菌 HdrRM LytTR 调节系统的调节控制通过膜隔离机制发挥作用。

细菌通过几大类感觉信号转导系统感知和响应环境变化。最近，我们描述了以前未被认识但广泛保守的一类原核感觉系统的关键特征，我们将其称为 LytTR 调节系统 (LRS)。我们之前的研究表明，大多数（如果不是全部）原核 LRS 膜蛋白可作为其同源转录调节因子的抑制剂，但迄今为止所采用的抑制机制仍然是个谜。使用变形链球菌HdrRM LRS 作为模型，我们展示了 LRS 膜蛋白 HdrM 如何通过将 HdrR 紧密隔离在膜定位的异聚 HdrR/M 复合物中来抑制其同源转录调节因子 HdrR。HdrR 的膜隔离阻止了 HdrR 的正反馈自动调节功能，从而保持了hdrRM操纵子的低基础表达。然而，这种机制可以通过异位表达竞争性抑制剂突变形式的 HdrR 来拮抗，该突变形式缺乏其 DNA 结合能力，同时仍保留其 HdrM 相互作用。我们的结果表明，HdrR 的隔离可能是抑制其转录调节功能所需的唯一机制，这表明 HdrRM LRS 的内源性激活可能是通过调节 HdrR/M 相互作用来实现的。

更新日期：2020-07-24

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