Ferric Citrate Regulator FecR Is Translocated across the Bacterial Inner Membrane via a Unique Twin-Arginine Transport-Dependent Mechanism.
Ferric Citrate Regulator FecR Is Translocated across the Bacterial Inner Membrane via a Unique Twin-Arginine Transport-Dependent Mechanism.
复制标题
柠檬酸铁调节剂 FecR 通过独特的双精氨酸运输依赖机制跨细菌内膜转运。
DOI：
10.1128/jb.00541-19
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发表时间：
2020
影响因子：
3.2
通讯作者：
Passmore IJ
中科院分区：
文献类型：
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作者：
Passmore IJ
在大肠杆菌中，柠檬酸盐介导的铁转运是获得铁的关键非血红素途径。柠檬酸铁与外膜蛋白FecA的结合诱导信号级联，最终激活细胞质σ因子FecI，导致fecABCD柠檬酸铁转运基因的转录。该过程的中心是由内膜蛋白FecR介导的信号转导。FecR通过单个跨膜螺旋跨越内膜，该跨膜螺旋在N和C末端侧接有细胞质和周质定向的部分。FecR的跨膜螺旋类似于双精氨酸信号序列，并且共有基序的成对精氨酸残基的取代使FecR-FecI信号级联放大，使得细胞在柠檬酸铁上生长时不能激活fecoperon的转录。此外，β-内酰胺酶C-末端与FecR跨膜螺旋的融合导致C-末端结构域的易位，其依赖于双精氨酸易位（达特）系统。我们的研究结果表明，FecR属于一个选择组的bitopic内膜蛋白，包含一个内部的双精氨酸信号sequence.IMPORTANCEIron是必不可少的几乎所有的生物体，由于其在代谢过程中的作用，并作为许多酶的辅因子。FecRI信号转导途径调节许多革兰氏阴性菌（包括大肠杆菌）中柠檬酸盐介导的铁输入。FecR与外膜蛋白FecA和细胞质抗σ因子FecI的相互作用已被广泛研究。然而，FecR插入膜的机制以前没有报道。在这项研究中，我们证明，FecR的细胞质膜的靶向依赖于达特系统。因此，FecR代表一类新的具有内部双精氨酸信号序列的双位Tat依赖性膜蛋白。
In Escherichia coli, citrate-mediated iron transport is a key nonheme pathway for the acquisition of iron. Binding of ferric citrate to the outer membrane protein FecA induces a signal cascade that ultimately activates the cytoplasmic sigma factor FecI, resulting in transcription of thefecABCDEferric citrate transport genes. Central to this process is signal transduction mediated by the inner membrane protein FecR. FecR spans the inner membrane through a single transmembrane helix, which is flanked by cytoplasm- and periplasm-orientated moieties at the N and C termini. The transmembrane helix of FecR resembles a twin-arginine signal sequence, and the substitution of the paired arginine residues of the consensus motif decouples the FecR-FecI signal cascade, rendering the cells unable to activate transcription of thefecoperon when grown on ferric citrate. Furthermore, the fusion of beta-lactamase C-terminal to the FecR transmembrane helix results in translocation of the C-terminal domain that is dependent on the twin-arginine translocation (Tat) system. Our findings demonstrate that FecR belongs to a select group of bitopic inner membrane proteins that contain an internal twin-arginine signal sequence.IMPORTANCEIron is essential for nearly all living organisms due to its role in metabolic processes and as a cofactor for many enzymes. The FecRI signal transduction pathway regulates citrate-mediated iron import in many Gram-negative bacteria, including Escherichia coli. The interactions of FecR with the outer membrane protein FecA and cytoplasmic anti-sigma factor FecI have been extensively studied. However, the mechanism by which FecR inserts into the membrane has not previously been reported. In this study, we demonstrate that the targeting of FecR to the cytoplasmic membrane is dependent on the Tat system. As such, FecR represents a new class of bitopic Tat-dependent membrane proteins with an internal twin-arginine signal sequence.