Catabolite activator protein: DNA binding and transcription activation

Lawson, Catherine L.; Swigon, David; Murakami, Katsuhiko; Darst, Seth A.; Berman, Helen M.; Ebright, Richard H.

doi:10.1016/j.sbi.2004.01.012

Cited by 295 publications

(345 citation statements)

References 64 publications

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“…25), or near the RNA exit channel, as observed for Rrn3 (refs 29, 34), the Pol II initiation factor TFIIB that stimulates RNA chain initiation allosterically 47 , and the Pol II coactivator Mediator 48 . The bacterial regulator catabolite activator protein 49 and the growth regulator ppGpp also bind at the RNA exit channel, and the latter was suggested to influence polymerase activity by modulating the coreshelf interface 50 .…”

Section: Discussionmentioning

confidence: 99%

RNA polymerase I structure and transcription regulation

Engel

Sainsbury

Cheung

et al. 2013

Nature

199

305

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Transcription of ribosomal RNA by RNA polymerase (Pol) I initiates ribosome biogenesis and regulates eukaryotic cell growth. The crystal structure of Pol I fromthe yeast Saccharomyces cerevisiae at 2.8A˚ resolution reveals all 14 subunits of the 590-kilodalton enzyme, and shows differences to Pol II. An ‘expander’ element occupies the DNA template site and stabilizes an expanded active centre cleft with an unwound bridge helix. A ‘connector’ element invades the cleft of an adjacent polymerase and stabilizes an inactive polymerase dimer. The connector and expander must detach during Pol I activation to enable transcription initiation and cleft contraction by convergent movement of the polymerase ‘core’ and ‘shelf’ modules. Conversion between an inactive expanded and an active contracted polymerase state may generally underlie transcription. Regulatory factors can modulate the core–shelf interface that includes a ‘composite’ active site for RNA chain initiation, elongation, proofreading and termination

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Section: Discussionmentioning

confidence: 99%

RNA polymerase I structure and transcription regulation

Engel

Sainsbury

Cheung

et al. 2013

Nature

199

305

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“…T ranscription factors, promoter sequences, and regulatory circuit architecture are often referred as "the regulatory genome" (27,33), and transcription factors are central to the function of regulatory networks (5). Organisms rely on regulatory networks to orchestrate the transcription of genes in response to internal or external environmental changes in order to optimize metabolism and enhance survival.…”

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confidence: 99%

“…The characteristic structure of Crp/Fnr is a C-terminal helix-turn-helix (HTH) motif that fits the DNA major groove and an N-terminal nucleotide binding domain (34). This class of transcriptional factors is named after the first two representatives discovered in Escherichia coli, i.e., the Crp (cyclic AMP [cAMP] receptor protein) and Fnr (fumarate and nitrate reductase regulator protein) (4,21,24,27). Crp/Fnr regulators are generally classified into different subfamilies (e.g., CooA, Crp, Dnr, FixK, Fnr, HbaR, NnrR, etc.)…”

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confidence: 99%

Functional Characterization of Crp/Fnr-Type Global Transcriptional Regulators in Desulfovibrio vulgaris Hildenborough

Zhou

Chen

Zane

et al. 2012

Appl Environ Microbiol

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Crp/Fnr-type global transcriptional regulators regulate various metabolic pathways in bacteria and typically function in response to environmental changes. However, little is known about the function of four annotated Crp/Fnr homologs (DVU0379, DVU2097, DVU2547, and DVU3111) in Desulfovibrio vulgaris Hildenborough. A systematic study using bioinformatic, transcriptomic, genetic, and physiological approaches was conducted to characterize their roles in stress responses. Similar growth phenotypes were observed for the crp/fnr deletion mutants under multiple stress conditions. Nevertheless, the idea of distinct functions of Crp/Fnr-type regulators in stress responses was supported by phylogeny, gene transcription changes, fitness changes, and physiological differences. The four D. vulgaris Crp/Fnr homologs are localized in three subfamilies (HcpR, CooA, and cc). The crp/fnr knockout mutants were well separated by transcriptional profiling using detrended correspondence analysis (DCA), and more genes significantly changed in expression in a ⌬DVU3111 mutant (JW9013) than in the other three paralogs. In fitness studies, strain JW9013 showed the lowest fitness under standard growth conditions (i.e., sulfate reduction) and the highest fitness under NaCl or chromate stress conditions; better fitness was observed for a ⌬DVU2547 mutant (JW9011) under nitrite stress conditions and a ⌬DVU2097 mutant (JW9009) under air stress conditions. A higher Cr(VI) reduction rate was observed for strain JW9013 in experiments with washed cells. These results suggested that the four Crp/Fnr-type global regulators play distinct roles in stress responses of D. vulgaris. DVU3111 is implicated in responses to NaCl and chromate stresses, DVU2547 in nitrite stress responses, and DVU2097 in air stress responses.T ranscription factors, promoter sequences, and regulatory circuit architecture are often referred as "the regulatory genome" (27, 33), and transcription factors are central to the function of regulatory networks (5). Organisms rely on regulatory networks to orchestrate the transcription of genes in response to internal or external environmental changes in order to optimize metabolism and enhance survival. Crp/Fnr regulators are global transcriptional regulators widely distributed in bacteria. The characteristic structure of Crp/Fnr is a C-terminal helix-turn-helix (HTH) motif that fits the DNA major groove and an N-terminal nucleotide binding domain (34). This class of transcriptional factors is named after the first two representatives discovered in Escherichia coli, i.e., the Crp (cyclic AMP [cAMP] receptor protein) and Fnr (fumarate and nitrate reductase regulator protein) (4, 21, 24, 27). Crp/Fnr regulators are generally classified into different subfamilies (e.g., CooA, Crp, Dnr, FixK, Fnr, HbaR, NnrR, etc.) according to phylogenetic affiliations (50). The increasing number of sequenced whole genomes has added to a growing list of Crp/Fnr family regulators identified in bacteria (9, 26); however, functions for most are not well defin...

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“…Our findings reported here are a successful attempt of studying CBD-A of the R-subunit by multidimensional solution NMR methods. Furthermore, the proposed model defines a mechanism that is highly conserved and thus relevant for cAMP recognition in other homologous CBDs coupled to effector proteins with diverse functions, such as transcription factors (catabolite-activator protein) (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), guanine nucleotide exchange factors (11), and ion channel proteins (both hyperpolarization-activated cyclic nucleotide-dependent channels and cyclic nucleotide-gated channels) (32,33). This model also serves as a general paradigm for how small molecules such as cAMP allosterically control large proteinprotein interfaces.…”

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confidence: 99%

cAMP activation of PKA defines an ancient signaling mechanism

Das

Esposito

Abu-Abed

et al. 2007

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

115

106

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allostery ͉ NMR ͉ cyclic nucleotide binding domain T he cAMP binding domain (CBD) and cAMP are conserved from bacteria to humans as a ubiquitous signaling mechanism to translate extracellular stress signals into appropriate biological responses (1). The major receptor for cAMP in higher eukaryotes, cAMP-dependent PKA (2), is ubiquitous in mammalian cells where it exists in two forms: the inactive tetrameric holoenzyme and the active dissociated catalytic subunit (Csubunit). In the inactive holoenzyme, two C-subunits are bound to a dimeric regulatory subunit (R-subunit) (Fig. 1a). Upon binding cAMP, the R-subunits undergo a conformational change that unleashes the active C-subunits (3, 4). The Rsubunits are composed of an N-terminal dimerization/docking domain, a flexible linker that includes an autoinhibitory segment, and two tandem CBDs (CBD-A and CBD-B; Fig. 1b) (5). The CBD-A of the isoform I␣ of the R-subunit of PKA (RI␣) contains a noncontiguous ␣-subdomain, which mediates the interactions with the C-subunit and a contiguous ␤-subdomain that forms a ␤-sandwich and contains the cAMP binding pocket (i.e., the phosphate binding cassette or PBC) ( Fig. 1 c and d) (6).Crystal structures of CBD-A of RI␣ in its cAMP-(6) and C-bound (7) states have revealed two very different conformations, highlighting the conformational plasticity of this ancient domain. Although these static crystal structures define two stable end points, questions remain about the allosteric control of the reversible shuttling between the two states. How does the signal generated by cAMP binding to the PBC (Fig. 1 c and d) propagate through a long-range allosteric network that spans both ␣-and ␤-subdomains? Previous analyses (8-16) have led to the proposal of an initial allosteric model in which the ␣-and ␤-subdomains are directly coupled to each other through a salt bridge between E200 and R241 and also possibly through a hydrophobic hinge defined by the L203, I204, and Y229 side-chain cluster (9,11,12). However, mutations (17), sequence conservation analyses (1), structurebased comparisons (1), and genetic screening (18,19) indicate that several other sites, which are not accounted for by the existing model, are also likely to play an active role in the cAMP-mediated activation of PKA. To comprehensively understand this allosteric mechanism, it is therefore necessary to elucidate at high resolution how cAMP remodels the free energy landscape of CBD-A, which serves as the central controlling unit of PKA. For this purpose, we have investigated by NMR RI␣ (residues 119-244), a construct that spans both ␣-and ␤-subdomains of CBD-A and retains high-

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Catabolite activator protein: DNA binding and transcription activation

Cited by 295 publications

References 64 publications

RNA polymerase I structure and transcription regulation

RNA polymerase I structure and transcription regulation

Functional Characterization of Crp/Fnr-Type Global Transcriptional Regulators in Desulfovibrio vulgaris Hildenborough

cAMP activation of PKA defines an ancient signaling mechanism

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