Atypical OmpR/PhoB Subfamily Response Regulator GlnR of Actinomycetes Functions as a Homodimer, Stabilized by the Unphosphorylated Conserved Asp-focused Charge Interactions

Lin, Wei; Wang, Ying; Han, Xiaobiao; Zhang, Zilong; Wang, Chengyuan; Wang, Jin; Yang, Huaiyu; Lü, Yinhua; Jiang, Weihong; Zhao, Guoping; Zhang, Peng

doi:10.1074/jbc.m113.543504

Cited by 37 publications

(46 citation statements)

References 53 publications

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“…RamR from S. coelicolor appears to be similar in this regard (Hudson and Nodwell, ; O'Connor and Nodwell, ). Attempts at phosphorylating the aspartate residue in vitro using phosphoramidate were unsuccessful and phos‐tag analysis failed to demonstrate a phosphorylated GlnR from either A. mediterranei or S. coelicolor (Lin et al ., ). The difficulty with a negative result is that the phos‐tag barely detects PhoP∼P (Lin et al ., ) or OmpR∼P (Adediran et al ., ) in vivo , so a low level of GlnR∼P might have simply gone undetected in these studies.…”

Section: Introductionmentioning

confidence: 97%

“…The difficulty with a negative result is that the phos‐tag barely detects PhoP∼P (Lin et al ., ) or OmpR∼P (Adediran et al ., ) in vivo , so a low level of GlnR∼P might have simply gone undetected in these studies. However, the crystal structures confirm an inadequate phosphorylation pocket (Lin et al ., ). Mutants that were unable to dimerize could not grow on minimal media in the presence of nitrate, nor were the GlnR gene targets activated, suggesting that phosphorylation‐independent homodimerization was sufficient to activate GlnR (Fig.…”

Section: Introductionmentioning

confidence: 99%

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To ∼P or Not to ∼P? Non‐canonical activation by two‐component response regulators

Desai

Kenney

2016

Molecular Microbiology

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Summary Bacteria sense and respond to their environment through the use of two-component regulatory systems. The ability to adapt to a wide range of environmental stresses is directly related to the number of two-component systems an organism possesses. Recent advances in this area have identified numerous variations on the archetype systems that employ a sensor kinase and a response regulator. It is now evident that many orphan regulators that lack cognate kinases do not rely on phosphorylation for activation and new roles for unphosphorylated response regulators have been identified. The significance of recent findings and suggestions for further research are discussed.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

To ∼P or Not to ∼P? Non‐canonical activation by two‐component response regulators

Desai

Kenney

2016

Molecular Microbiology

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“…Phosphorylation-independent dimerization and activity has been observed for a variety of response regulators [61]. In some instances, a conserved non-phosphorylated aspartate residue is required for dimerization and full activity [64]. This may be the case with ClaR, with the modest decrease in activity for the D193A claR allele due to the lack of proper intermolecular interactions.…”

Section: Phosphorylation and Clar Functionmentioning

confidence: 97%

The Agrobacterium tumefaciens CheY-like protein ClaR regulates biofilm formation

Feirer

Kim

et al. 2017

Microbiology

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The switch from a motile, planktonic existence to an attached biofilm is a major bacterial lifestyle transition that is often mediated by complex regulatory pathways. In this report, we describe a CheY-like protein required for control of the motileto-sessile switch in the plant pathogen Agrobacterium tumefaciens. This regulator, which we have designated ClaR, possesses two distinct CheY-like receiver (REC) domains and is involved in the negative regulation of biofilm formation, through production of the unipolar polysaccharide (UPP) adhesin and cellulose. The ClaR REC domains share predicted structural homology with characterized REC domains and contain the majority of active site residues known to be essential for protein phosphorylation. REC1 is missing the conserved aspartate (N72) residue and although present in REC 2 (D193), it is not required for ClaR-dependent regulation suggesting that phosphorylation, which modulates the activity of many CheYlike proteins, appears not to be essential for ClaR activity. We also show that ClaR-dependent negative regulation of attachment is diminished significantly in mutants for PruA and PruR, proteins known to be involved in a pterin-mediated attachment regulation pathway. In A. tumefaciens, pterins are required for control of the intracellular signal cyclic diguanylate monophosphate through the DcpA regulator, but our findings suggest that pterin-dependent ClaR control of attachment can function independently from DcpA, including dampening of c-di-GMP levels. This report of a novel CheY-type biofilm regulator in A. tumefaciens thus also adds significant details to the role of pterin-mediated signalling.

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“…The OmpR/PhoB ARR GlnR was recently reported in actinomycetes. This is an orphan RR that globally coordinates the expression of genes related to nitrogen metabolism (Lin et al 2014). GlnR Asp50 in the N-terminal receiver domain is unphosphorylated but is necessary for interaction with Arg52 and Thr9 to maintain the proper conformation for homodimerization.…”

Section: Phosphorylation-independent Activation and Atypical Rrsmentioning

confidence: 99%

Prokaryotic 2-component systems and the OmpR/PhoB superfamily

et al. 2015

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Abstract:In bacteria, 2-component regulatory systems (TCSs) are the critical information-processing pathways that link stimuli to specific adaptive responses. Signals perceived by membrane sensors, which are generally histidine kinases, are transmitted by response regulators (RRs) to allow cells to cope rapidly and effectively with environmental challenges. Over the past few decades, genes encoding components of TCSs and their responsive proteins have been identified, crystal structures have been described, and signaling mechanisms have been elucidated. Here, we review recent findings and interesting breakthroughs in bacterial TCS research. Furthermore, we discuss structural features, mechanisms of activation and regulation, and cross-regulation of RRs, with a focus on the largest RR family, OmpR/PhoB, to provide a comprehensive overview of these critically important signaling molecules.

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Atypical OmpR/PhoB Subfamily Response Regulator GlnR of Actinomycetes Functions as a Homodimer, Stabilized by the Unphosphorylated Conserved Asp-focused Charge Interactions

Cited by 37 publications

References 53 publications

To ∼P or Not to ∼P? Non‐canonical activation by two‐component response regulators

To ∼P or Not to ∼P? Non‐canonical activation by two‐component response regulators

The Agrobacterium tumefaciens CheY-like protein ClaR regulates biofilm formation

Prokaryotic 2-component systems and the OmpR/PhoB superfamily

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