Crystal Structure of the Intermediate Complex of the Arginine Repressor from Mycobacterium tuberculosis Bound with Its DNA Operator Reveals Detailed Mechanism of Arginine Repression

Cherney, Leonid T.; Cherney, M.M.; Garen, Craig R.; James, Michael N.G.

doi:10.1016/j.jmb.2010.03.065

Cited by 13 publications

(9 citation statements)

References 38 publications

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“…The conformational differences observed between holoBsArgR and apoBsArgR in the positions of their DNA-binding domains may be related to the mechanism of activation of DNA by L-arg binding. To evaluate this possibility the structure of holoBsArgR in the final 500 ns of the simulation was compared with known requirements for DNA binding based on biochemical evidence for EcArgR [ 9 , 21 , 22 ] and crystal structures of other ArgR-DNA complexes [ 7 , 10 , 11 , 12 ]. In a crystal structure of two isolated N-terminal domains of BsArgR bound to a short palindromic DNA duplex (PDB ID: 2P5L) the major groove in successive openings on one “face” of the DNA is occupied by two N-terminal domains, with key residue Arg43 of each domain contacting symmetry-equivalent guanine residues of the palindromic sequence.…”

Section: Resultsmentioning

confidence: 99%

“…However, the low sequence conservation among ArgRs makes the boundaries between the domains and the linker difficult to assign with confidence ( Figure 1 ), despite the availability of intact ArgR crystal structures from several organisms. The interdomain regions of B. stearothermophilus ArgR (BstArgR, Protein Data Bank (PDB) ID: 1B4A; [ 4 ]), B. subtilis ArgR (BsArgR, PDB ID: 1F9N; [ 5 , 10 ]), and Mycobacterium tuberculosis ArgR (MtArgR, PDB ID: 3FHZ, 3LAJ; [ 11 , 12 ]) present an irregularly structured segment followed by a 3-turn alpha helix, α4. In E. coli , however, ten of the 17 residues in the interdomain segment have low or very low helix propensity (Pro, Gly, Val, Thr, Ser, Asn), making a 3-turn alpha helix improbable.…”

Section: Introductionmentioning

confidence: 99%

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Conserved Dynamic Mechanism of Allosteric Response to L-arg in Divergent Bacterial Arginine Repressors

et al. 2020

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Hexameric arginine repressor, ArgR, is the feedback regulator of bacterial L-arginine regulons, and sensor of L-arg that controls transcription of genes for its synthesis and catabolism. Although ArgR function, as well as its secondary, tertiary, and quaternary structures, is essentially the same in E. coli and B. subtilis, the two proteins differ significantly in sequence, including residues implicated in the response to L-arg. Molecular dynamics simulations are used here to evaluate the behavior of intact B. subtilis ArgR with and without L-arg, and are compared with prior MD results for a domain fragment of E. coli ArgR. Relative to its crystal structure, B. subtilis ArgR in absence of L-arg undergoes a large-scale rotational shift of its trimeric subassemblies that is very similar to that observed in the E. coli protein, but the residues driving rotation have distinct secondary and tertiary structural locations, and a key residue that drives rotation in E. coli is missing in B. subtilis. The similarity of trimer rotation despite different driving residues suggests that a rotational shift between trimers is integral to ArgR function. This conclusion is supported by phylogenetic analysis of distant ArgR homologs reported here that indicates at least three major groups characterized by distinct sequence motifs but predicted to undergo a common rotational transition. The dynamic consequences of L-arg binding for transcriptional activation of intact ArgR are evaluated here for the first time in two-microsecond simulations of B. subtilis ArgR. L-arg binding to intact B. subtilis ArgR causes a significant further shift in the angle of rotation between trimers that causes the N-terminal DNA-binding domains lose their interactions with the C-terminal domains, and is likely the first step toward adopting DNA-binding-competent conformations. The results aid interpretation of crystal structures of ArgR and ArgR-DNA complexes.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conserved Dynamic Mechanism of Allosteric Response to L-arg in Divergent Bacterial Arginine Repressors

et al. 2020

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“…deviation of 1.0 Å for 80 equivalent Cα in residues 4–149, and Z-score of 17.2), (ii) Bsu AhrC [ 8 ] (PDB entry 1F9N; r.m.s. deviation of 4.7 Å for 102 equivalent Cα in residues 4–149, and Z-score of 17.2), and (iii) Mtb ArgR [ 10 ] (PDB entry 3LAP; r.m.s. deviation of 6.0 Å for 114 equivalent Cα in residues 4–149, and Z-score of 15.4).…”

Section: Resultsmentioning

confidence: 99%

Structural Analysis and Insights into the Oligomeric State of an Arginine-Dependent Transcriptional Regulator from Bacillus halodurans

et al. 2016

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The arginine repressor (ArgR) is an arginine-dependent transcription factor that regulates the expression of genes encoding proteins involved in the arginine biosynthesis and catabolic pathways. ArgR is a functional homolog of the arginine-dependent repressor/activator AhrC from Bacillus subtilis, and belongs to the ArgR/AhrC family of transcriptional regulators. In this research, we determined the structure of the ArgR (Bh2777) from Bacillus halodurans at 2.41 Å resolution by X-ray crystallography. The ArgR from B. halodurans appeared to be a trimer in a size exclusion column and in the crystal structure. However, it formed a hexamer in the presence of L-arginine in multi-angle light scattering (MALS) studies, indicating the oligomerization state was dependent on the presence of L-arginine. The trimeric structure showed that the C-terminal domains form the core, which was made by inter-subunit interactions mainly through hydrophobic contacts, while the N-terminal domains containing a winged helix-turn-helix DNA binding motif were arranged around the periphery. The arrangement of trimeric structure in the B. halodurans ArgR was different from those of other ArgR homologs previously reported. We finally showed that the B. halodurans ArgR has an arginine-dependent DNA binding property by an electrophoretic mobility shift assay.

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“… Variety of one-component TFs found in nature. (A) ArgR (3LAJ, Cherney et al, 2010 ) represses the transcription of the biosynthetic genes of the arginine operon. ArgR is a wHTH transcriptional aporepressor activated by the corepressor arginine, so that the regulated operon is not transcribed when the effector is present.…”

Section: Effector Binding Domainmentioning

confidence: 99%

Transcription factor-based biosensors enlightened by the analyte

et al. 2015

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Whole cell biosensors (WCBs) have multiple applications for environmental monitoring, detecting a wide range of pollutants. WCBs depend critically on the sensitivity and specificity of the transcription factor (TF) used to detect the analyte. We describe the mechanism of regulation and the structural and biochemical properties of TF families that are used, or could be used, for the development of environmental WCBs. Focusing on the chemical nature of the analyte, we review TFs that respond to aromatic compounds (XylS-AraC, XylR-NtrC, and LysR), metal ions (MerR, ArsR, DtxR, Fur, and NikR) or antibiotics (TetR and MarR). Analyzing the structural domains involved in DNA recognition, we highlight the similitudes in the DNA binding domains (DBDs) of these TF families. Opposite to DBDs, the wide range of analytes detected by TFs results in a diversity of structures at the effector binding domain. The modular architecture of TFs opens the possibility of engineering TFs with hybrid DNA and effector specificities. Yet, the lack of a crisp correlation between structural domains and specific functions makes this a challenging task.

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Crystal Structure of the Intermediate Complex of the Arginine Repressor from Mycobacterium tuberculosis Bound with Its DNA Operator Reveals Detailed Mechanism of Arginine Repression

Cited by 13 publications

References 38 publications

Conserved Dynamic Mechanism of Allosteric Response to L-arg in Divergent Bacterial Arginine Repressors

Conserved Dynamic Mechanism of Allosteric Response to L-arg in Divergent Bacterial Arginine Repressors

Structural Analysis and Insights into the Oligomeric State of an Arginine-Dependent Transcriptional Regulator from Bacillus halodurans

Transcription factor-based biosensors enlightened by the analyte

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