Structural basis of copper-efflux-regulator-dependent transcription activation

Shi, Wanliang; Zhang, Baoyue; Jiang, Yanan; Liu, Chang; Zhou, Wei; Chen, Ming; Yang, Yang; Hu, Yangbo; Liu, Bin

doi:10.1016/j.isci.2021.102449

Cited by 21 publications

(12 citation statements)

References 46 publications

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“…In general, these results show the value of systematic concentration‐dependent measurements to incisively identify the relationship of structure to function. Bending of the DNA in presence of Cu(I) and bound RNAP was also demonstrated by a recent cryo‐EM structure 13 …”

Section: Introductionmentioning

confidence: 69%

“…11 In this bent state, RNA polymerase can interact with the CueR-DNA complex and initiate the transcription process. 7,13 Single-molecule FRET (smFRET) measurements have shown that in solution, CueR can exist in four different states: apo-CueR, holo-CueR, apo-CueR bound to DNA, and holo-CueR bound to DNA. 14 Initiation of transcription occurs when holo-CueR is bound to the DNA, and termination occurs when holo-CueR bound to the DNA is replaced by apo-CueR.…”

Section: Introductionmentioning

confidence: 99%

“…Bending of the DNA in presence of Cu(I) and bound RNAP was also demonstrated by a recent cryo-EM structure. 13 The crystallographic data report changes in the DNA binding domain of the protein (Figure 1) between the repressed-and active-state of CueR. 12 We have also applied electron paramagnetic resonance (EPR) distance measurements to follow conformational changes that CueR undergoes as a function of Cu(I) and DNA binding in solution.…”

Section: Introductionmentioning

confidence: 99%

“…However, the presence of Cu(I) is critical in order to facilitate bending of the DNA 11 . In this bent state, RNA polymerase can interact with the CueR‐DNA complex and initiate the transcription process 7,13 …”

Section: Introductionmentioning

confidence: 99%

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Allostery‐driven changes in dynamics regulate the activation of bacterial copper transcription factor

et al. 2022

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Metalloregulators bind and respond to metal ions by regulating the transcription of metal homeostasis genes. Copper efflux regulator (CueR) is a copper‐responsive metalloregulator that is found in numerous Gram‐negative bacteria. Upon Cu(I) coordination, CueR initiates transcription by bending the bound DNA promoter regions facilitating interaction with RNA polymerase. The structure of Escherichia coli CueR in presence of DNA and metal ion has been reported using X‐ray crystallography and cryo‐EM, providing information about the mechanism of action. However, the specific role of copper in controlling this transcription mechanism remains elusive. Herein, we use room temperature electron paramagnetic resonance (EPR) experiments to follow allosterically driven dynamical changes in E. coli CueR induced by Cu(I) binding. We suggest that more than one Cu(I) ion binds per CueR monomer, leading to changes in site‐specific dynamics at the Cu(I) binding domain and at the distant DNA binding site. Interestingly, Cu(I) binding leads to an increase in dynamics about 27 Å away at the DNA binding domain. These changes in the dynamics of the DNA binding domain are important for exact coordination with the DNA. Thus, Cu(I) binding is critical to initiate a series of conformational changes that regulate and initiate gene transcription. Broad audience statement The dynamics of metal transcription factors as a function of metal and DNA binding are complex. In this study, we use EPR spectroscopy to measure dynamical changes of Escherichia coli CueR as a function of copper and DNA binding. We show that copper controls the activation of the transcription processes by initiation a series of dynamical changes over the protein.

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Section: Introductionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Allostery‐driven changes in dynamics regulate the activation of bacterial copper transcription factor

et al. 2022

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“…[1,8] The coordination of cognate metal ions (i. e. Cu I , Ag I and Au I ) to CueR and the mechanism of the allosteric regulation are well understood from solution phase, cryo-EM and crystallographic studies. [8][9][10][11][12][13][14] Any of these cognate metal ions coordinate to the Cys112 and Cys120 cysteine residues in an identical, linear fashion stabilizing the structure of the metal binding loop and a short helix. [8,10] Both the overall dimeric protein structure and the local metal ion environment is essentially the same in the Cu I -and the Ag I -bound CueR forms, with the exception of longer metal sulfur distances for Ag I .…”

Section: Introductionmentioning

confidence: 99%

Tying Up a Loose End: On the Role of the C‐Terminal CCHHRAG Fragment of the Metalloregulator CueR

et al. 2022

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The transcriptional regulator CueR is activated by the binding of Cu I , Ag I , or Au I to two cysteinates in a near-linear fashion. The C-terminal CCHHRAG sequence in Escherichia coli CueR present potential additional metal binding ligands and here we explore the effect of deleting this fragment on the binding of Ag I to CueR. CD spectroscopic and ESI-MS data indicate that the high Ag I -binding affinity of WT-CueR is significantly reduced in Δ7C-CueR. [111 Ag PAC spectroscopy demonstrates that the WT-CueR metal site structure (AgS 2 ) is conserved, but less populated in the truncated variant. Thus, the function of the Cterminal fragment may be to stabilize the two-coordinate metal site for cognate monovalent metal ions. In a broader perspective this is an example of residues beyond the second coordination sphere affecting metal site physicochemical properties while leaving the structure unperturbed.

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Recent Developments in Terahertz Nanosensors

Bahk,

Kim,

Ahn

et al. 2023

Advanced Photonics Research

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Terahertz (THz) waves occupy the electromagnetic spectrum between microwave and infrared radiation, with frequencies typically ranging from 0.1 to 10 THz. Compared with other optic and electronic tools, this frequency range allows for unique sensing applications such as nondestructive, label‐free, and fast detection. Despite the promising features of THz sensing applications, the dimensional mismatch between THz wavelength and nanoscale agents hinders practical applications, especially in biosensing and chemical sensing. Several recent studies propose that engineered THz resonators, such as split ring resonators, linear dipole and slot antennas, and nanogap loop antennas, enhance the sensitivity for detecting trace amounts of target molecules, such as viruses and explosives. When combined with near‐field imaging techniques in the THz range, these THz nanosensors may revolutionize our understanding of complex nanoscale systems, including 2D materials, as researchers can observe quantum dynamics directly in molecules, mobile carriers in semiconductors, THz quantum nonlocal effects, and dynamics of excitons and polaritons at THz frequencies. Additionally, THz biomolecular sensors are also discussed, where the sensor platforms will lead to a great impact in the advancement of ultrasmall‐quantity characterization of proteins, label‐free diagnosis of Alzheimer's disease, and conformational dynamics of biomolecules in their aqueous environment.

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Structural basis of copper-efflux-regulator-dependent transcription activation

Abstract: HighlightsCryo-EM structures of intact CueR-TAC complex without and with RNA synthesis CueR dimer activates transcription through bending promoter DNAThe structures reveal the interactions between sNCR and CueRThe sNCR/CueR interactions play an auxiliary role in CueRdependent transcription

Cited by 21 publications

References 46 publications

Allostery‐driven changes in dynamics regulate the activation of bacterial copper transcription factor

Allostery‐driven changes in dynamics regulate the activation of bacterial copper transcription factor

Tying Up a Loose End: On the Role of the C‐Terminal CCHHRAG Fragment of the Metalloregulator CueR

Recent Developments in Terahertz Nanosensors

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