Structural overview on the allosteric activation of cyclic AMP receptor protein

Won, Hyung‐Sik; Lee, Yoo-Sup; Lee, Sung‐Hee; Lee, Bong-Jin

doi:10.1016/j.bbapap.2009.04.015

Cited by 54 publications

(78 citation statements)

References 70 publications

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“…Other Crp/Fnr family members, such as Crp in E. coli, use cAMP for activation (26). In E. coli, cAMPs bind at the N-terminal domain of both Crp monomers, where the antiparallel β-roll structure composes part of the cAMP binding site (27).…”

Section: Id Code 2beo] (12)mentioning

confidence: 99%

Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria

Hall

Grundström

Begum

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could fulfill this function. Here we report the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, the hly operator PrfA box motif. These structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell. The crystal structure of PrfA WT in complex only with DNA confirms that PrfA WT can adopt a DNA binding-compatible structure without binding the GSH activator molecule. By binding to PrfA in the cytosol of the host cell, GSH induces the correct fold of the HTH motifs, thus priming the PrfA protein for DNA interaction.PrfA | glutathione | activation | Listeria | virulence

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Section: Id Code 2beo] (12)mentioning

confidence: 99%

Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria

Hall

Grundström

Begum

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Although there is mounting evidence to suggest that the E. coli CRP undergoes allosteric conformational changes upon cAMP binding from a variety of spectroscopic and biochemical techniques (23)(24)(25)(26), little is known about the nature of the conformational change to the allosterically activated conformation in Mtb-CRP. Wild-type CRP is activated by cAMP only, although it can bind other cyclic nucleotides with comparable affinity (27).…”

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confidence: 99%

Structural Insights into the Mechanism of the Allosteric Transitions of Mycobacterium tuberculosis cAMP Receptor Protein

Reddy

Palaninathan

Bruning

et al. 2009

Journal of Biological Chemistry

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Mycobacterium tuberculosis (Mtb) 3 is thought to enter a latent phase (1) to survive hostile environments like starvation and hypoxia (2). During times of duress, transcriptional regulators belonging to the CRP/fumarate and nitrate reduction regulator family respond to a broad spectrum of intracellular and exogenous signals associated with low oxygen stress and starvation, modulating the expression of various metabolic genes in many facultative or strictly anaerobic bacteria (3, 4). In Escherichia coli, CRP controls the expression of over 100 genes in response to changes in the intracellular concentration of cAMP (5). CRP is activated by the binding of cAMP and subsequently becomes an active transcriptional regulator by means of allosteric structural changes (6 -10). Several essential genes are up-regulated during intracellular growth in macrophages (11), suggesting that cAMP signaling may be important to M. tuberculosis during its interaction with the host. Indeed, Rv3676 (Mtb-CRP), the CRP homolog in M. tuberculosis H37Rv, is a cAMP-responsive transcription factor (12-14). Deletion of Rv3676 results in impaired growth in laboratory medium, in bone marrow-derived macrophages, and in tubercle bacillus grown in a mouse model system (13). These observations suggest that Mtb-CRP plays a critical role in Mtb survival, especially in macrophages.Several models have been offered as possible explanations for how the sensory module can transmit the signal to the distant DNA-binding domain (9,(15)(16)(17). Perhaps the most intriguing question about the CRP family is how ligand binding within the effector domain can influence the properties of the DNA-binding domain. Answers to this question remain elusive, in part because the only CRP crystal structure available for Mtb is that of the cAMP-free form (18) The Mtb-CRP apo structure displayed asymmetry between the subunits as compared with the E. coli CRP⅐cAMP crystal structure, which shares only a 32% sequence identity with Mtb-CRP. Although the asymmetry observed in the apoMtb-CRP crystal (18) has been interpreted as an important factor in its mechanism, NMR studies in solution could not find any evidence of structural asymmetry in either the E. coli apoCRP or the cAMP⅐CRP (19 -21). In contrast, recent NMR studies (22) reported cAMP binding resulting in a coil to helix transition that extends the coil-coil dimerization and functions as a regulatory switch. Nevertheless, the allosteric mechanism by which ligand binding induces a conformational transition remains elusive from the same organism and atomic level structural comparisons are needed to fully understand the transition. The atomic coordinates and structure factors (codes 3I54 and 3I59) HTH, helix-turn-helix; r.m.s.d., root mean square deviation; CHES, 2-(cyclohexylamino)ethanesulfonic acid.

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“…The N termini of TDE2725 and TDE2726 contain a cNMP binding domain. This domain often binds cyclic nucleotide monophosphate (cAMP or cGMP) to activate protein functions (61)(62)(63). Both TDE0125 and TDE2659 harbor a GAF domain, which is named from the first three classes of proteins containing this domain: cGMP-specific phosphodiesterases, adenylyl cyclases, and FhlA (a 54 activator) (64).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Cyclic Di-GMP Binding Protein TDE0214 Affects the Motility, Biofilm Formation, and Virulence of Treponema denticola

Bian

et al. 2013

Journal of Bacteriology

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bAs a ubiquitous second messenger, cyclic dimeric GMP (c-di-GMP) has been studied in numerous bacteria. The oral spirochete Treponema denticola, a periodontal pathogen associated with human periodontitis, has a complex c-di-GMP signaling network. However, its function remains unexplored. In this report, a PilZ-like c-di-GMP binding protein (TDE0214) was studied to investigate the role of c-di-GMP in the spirochete. TDE0214 harbors a PilZ domain with two signature motifs: RXXXR and DXSXXG. Biochemical studies showed that TDE0214 binds c-di-GMP in a specific manner, with a dissociation constant (K d ) value of 1.73 M, which is in the low range compared to those of other reported c-di-GMP binding proteins. To reveal the role of c-di-GMP in T. denticola, a TDE0214 deletion mutant (Td⌬214) was constructed and analyzed in detail. First, swim plate and single-cell tracking analyses showed that Td⌬214 had abnormal swimming behaviors: the mutant was less motile and reversed more frequently than the wild type. Second, we found that biofilm formation of Td⌬214 was substantially repressed (ϳ6.0-fold reduction). Finally, in vivo studies using a mouse skin abscess model revealed that the invasiveness and ability to induce skin abscesses and host humoral immune responses were significantly attenuated in Td⌬214, indicative of the impact that TDE0214 has on the virulence of T. denticola. Collectively, the results reported here indicate that TDE0214 plays important roles in motility, biofilm formation, and virulence of the spirochete. This report also paves a way to further unveil the roles of the c-di-GMP signaling network in the biology and pathogenicity of T. denticola.

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Structural overview on the allosteric activation of cyclic AMP receptor protein

Cited by 54 publications

References 70 publications

Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria

Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria

Structural Insights into the Mechanism of the Allosteric Transitions of Mycobacterium tuberculosis cAMP Receptor Protein

Inactivation of Cyclic Di-GMP Binding Protein TDE0214 Affects the Motility, Biofilm Formation, and Virulence of Treponema denticola

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