An Lrp-type transcriptional regulator from Agrobacterium tumefaciens condenses more than 100 nucleotides of DNA into globular nucleoprotein complexes

Jafri, Samina; Evoy, Stéphane; Cho, Kyungyun; Craighead, Harold G.; Winans, Stephen C.

doi:10.1006/jmbi.1999.2715

Cited by 40 publications

(40 citation statements)

References 53 publications

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“…This result clearly indicates that AldR serves as a repressor for the regulation of its own gene. Most Lrp/AsnC family regulators are known to negatively regulate the expression of their own genes indepen- dently of effector molecules, thereby keeping their cellular levels in a steady state (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47).…”

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confidence: 99%

Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR

Jeong

Hyun

2015

J Bacteriol

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In the presence of alanine, AldR, which belongs to the Lrp/AsnC family of transcriptional regulators and regulates ald encoding alanine dehydrogenase in Mycobacterium smegmatis, changes its quaternary structure from a homodimer to an octamer with an open-ring conformation. Four AldR-binding sites (O2, O1, O4, and O3) with a consensus sequence of GA/T-N 2 -NWW/WWN-N 2 -A/TC were identified upstream of the M. smegmatis ald gene by means of DNase I footprinting analysis. O2, O1, and O4 are required for the induction of ald expression by alanine, while O3 is directly involved in the repression of ald expression. In addition to O3, both O1 and O4 are also necessary for full repression of ald expression in the absence of alanine, due to cooperative binding of AldR dimers to O1, O4, and O3. Binding of a molecule of the AldR octamer to the ald control region was demonstrated to require two AldR-binding sites separated by three helical turns between their centers and one additional binding site that is in phase with the two AldR-binding sites. The cooperative binding of AldR dimers to DNA requires three AldR-binding sites that are aligned with a periodicity of three helical turns. The aldR gene is negatively autoregulated independently of alanine. Comparative analysis of ald expression of M. smegmatis and Mycobacterium tuberculosis in conjunction with sequence analysis of both ald control regions led us to suggest that the expression of the ald genes in both mycobacterial species is regulated by the same mechanism. IMPORTANCEIn mycobacteria, alanine dehydrogenase (Ald) is the enzyme required both to utilize alanine as a nitrogen source and to grow under hypoxic conditions by maintaining the redox state of the NADH/NAD ؉ pool. Expression of the ald gene was reported to be regulated by the AldR regulator that belongs to the Lrp/AsnC (feast/famine) family, but the underlying mechanism was unknown. This study revealed the regulation mechanism of ald in Mycobacterium smegmatis and Mycobacterium tuberculosis. Furthermore, a generalized arrangement pattern of cis-acting regulatory sites for Lrp/AsnC (feast/famine) family regulators is suggested in this study. N AD(H)-dependent alanine dehydrogenase (Ald; EC 1.4.1.1) catalyzes the oxidative deamination of L-alanine to pyruvate and reversibly catalyzes the reductive amination of pyruvate to L-alanine. Ald is required for mycobacteria to utilize alanine as a nitrogen source via the oxidative deamination reaction (1-3). It was also proposed that Ald helps mycobacteria maintain the redox state of the NADH/NAD ϩ pool under respiration-inhibiting conditions, such as hypoxic conditions, by regenerating NAD ϩ from NADH via its reductive amination reaction (2, 4, 5). The enzyme forms a hexamer of identical subunits with the N-terminal catalytic domain and the C-terminal NAD(H)-binding domain (6, 7). Ald was shown to be one of the major antigens found in culture filtrates of Mycobacterium tuberculosis (8,9).Expression of the ald gene as well as the synthesis and activity of Ald we...

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Section: Figmentioning

confidence: 99%

Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR

Jeong

Hyun

2015

J Bacteriol

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“…However, it seems that LrpC possesses unusual properties among eubacterial DNA structuring proteins, including the Lrp-like family. Whereas E. coli Lrp has been proposed to wrap DNA (35), LrpC, along with the Smj12 protein from Sulfolobus solfataricus (which also overwinds DNA) and the PutR protein from Agrobacterium tumefaciens, are the only members of the Lrplike family for which DNA wrapping has been firmly demonstrated (36,37). Looped structures formed by LrpC where 80 bp of DNA is wrapped resemble eukaryotic dimers of (H 3 -H 4 ) and archaeal HMf or HTz tetrasomes ( Fig.…”

Section: Fig 4 Identification Of a Curved Region Of Pbr322 To Whichmentioning

confidence: 99%

Contribution of DNA Conformation and Topology in Right-handed DNA Wrapping by the Bacillus subtilis LrpC Protein

Beloin¹,

Jeusset²,

Révet³

et al. 2003

Journal of Biological Chemistry

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The Bacillus subtilis LrpC protein belongs to the Lrp/ AsnC family of transcriptional regulators. It binds the upstream region of the lrpC gene and autoregulates its expression. In this study, we have dissected the mechanisms that govern the interaction of LrpC with DNA by electrophoretic mobility shift assay, electron microscopy, and atomic force microscopy. LrpC is a structurespecific DNA binding protein that forms stable complexes with curved sequences containing phased A tracts and wraps DNA to form spherical, nucleosomelike structures. Formation of such wraps, initiated by cooperative binding of LrpC to DNA, results from optimal protein/protein interactions specified by the DNA conformation. In addition, we have demonstrated that LrpC constrains positive supercoils by wrapping the DNA in a right-handed superhelix, as visualized by electron microscopy.

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“…Primary sequence analysis predicts whether PutA proteins from other gram-negative bacteria also contain the RHH domain. Prokaryotes in which PutA lacks transcriptional repressor activity, such as Agrobacterium tumefaciens and Rhodobacter capsulatus, regulate proline utilization via transcriptional factors such as PutR, an Lrp-type activator protein which activates putA gene expression in response to increased proline levels (11,22,24). Besides contributing to cellular energy needs, proline metabolism has been shown to impact intracellular redox homeostasis in a variety of organisms such as fungal pathogens, yeast, and mammalian cells (10,13,36).…”

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confidence: 99%

Oxygen Reactivity of PutA from Helicobacter Species and Proline-Linked Oxidative Stress

Krishnan

Becker

2006

J Bacteriol

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An Lrp-type transcriptional regulator from Agrobacterium tumefaciens condenses more than 100 nucleotides of DNA into globular nucleoprotein complexes

Cited by 40 publications

References 53 publications

Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR

Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR

Contribution of DNA Conformation and Topology in Right-handed DNA Wrapping by the Bacillus subtilis LrpC Protein

Oxygen Reactivity of PutA from Helicobacter Species and Proline-Linked Oxidative Stress

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