arac transcription factor


Summary: A transcription factor found in BACTERIA that positively and negatively regulates the expression of proteins required for the uptake and catabolism of L-ARABINOSE.

Top Publications

  1. Ibarra J, Perez Rueda E, Segovia L, Puente J. The DNA-binding domain as a functional indicator: the case of the AraC/XylS family of transcription factors. Genetica. 2008;133:65-76 pubmed
    ..This approach would be useful in assigning regulatory roles to uncharacterized members of other transcriptional factor families and it might facilitate their experimental analysis. ..
  2. Carra J, Schleif R. Variation of half-site organization and DNA looping by AraC protein. EMBO J. 1993;12:35-44 pubmed
  3. Niland P, Hühne R, Müller Hill B. How AraC interacts specifically with its target DNAs. J Mol Biol. 1996;264:667-74 pubmed
    ..D256A binds to the double A-box, but not to the double B-box, in the presence of L-arabinose but not in its absence. The implications of these results for the mechanism of AraC induction by L-arabinose are discussed. ..
  4. Ma Z, Richard H, Tucker D, Conway T, Foster J. Collaborative regulation of Escherichia coli glutamate-dependent acid resistance by two AraC-like regulators, GadX and GadW (YhiW). J Bacteriol. 2002;184:7001-12 pubmed
    ..These complex control circuits impose tight rein over expression of the gadA and gadBC system yet provide flexibility for inducing acid resistance under many conditions that presage acid stress...
  5. Tramonti A, Visca P, De Canio M, Falconi M, De Biase D. Functional characterization and regulation of gadX, a gene encoding an AraC/XylS-like transcriptional activator of the Escherichia coli glutamic acid decarboxylase system. J Bacteriol. 2002;184:2603-13 pubmed
    ..Gel shift and DNase I footprinting analyses with a MalE-GadX fusion protein demonstrate that GadX binds gadA and gadBC promoters at different sites and with different binding affinities...
  6. Wu M, Schleif R. Strengthened arm-dimerization domain interactions in AraC. J Biol Chem. 2001;276:2562-4 pubmed
    ..Mutating the two positively charged residues to alanines individually and collectively decreased or eliminated the constitutivity created by the N16D mutation. ..
  7. Saviola B, Seabold R, Schleif R. Arm-domain interactions in AraC. J Mol Biol. 1998;278:539-48 pubmed
    ..When arabinose is added, the arms are pulled off the C-terminal domains, thereby releasing them to bind to adjacently located DNA half-sites and activate transcription. ..
  8. Opdyke J, Kang J, Storz G. GadY, a small-RNA regulator of acid response genes in Escherichia coli. J Bacteriol. 2004;186:6698-705 pubmed
  9. Zhang X, Reeder T, Schleif R. Transcription activation parameters at ara pBAD. J Mol Biol. 1996;258:14-24 pubmed
    ..On the pBAD promoter we obtained kinetic parameters of Kd = 0.3 nM and K2 = 1 minute(-1). The unusually tight binding of polymerase in the presence of AraC suggests that AraC binds polymerase tightly. ..

More Information


  1. Lobell R, Schleif R. DNA looping and unlooping by AraC protein. Science. 1990;250:528-32 pubmed
    ..Slight reorientation of the subunits of AraC could specify looping or unlooping by the protein. Such a mechanism could account for regulation of DNA looping in other systems. ..
  2. Ross J, Gryczynski U, Schleif R. Mutational analysis of residue roles in AraC function. J Mol Biol. 2003;328:85-93 pubmed
    ..Although the side-chain of residue 15 interacts directly with arabinose bound to the N-terminal dimerization domain, the properties of mutant F15L indicate that this mutation increases the affinity of the arm for the DNA-binding domain. ..
  3. Shin S, Castanie Cornet M, Foster J, Crawford J, Brinkley C, Kaper J. An activator of glutamate decarboxylase genes regulates the expression of enteropathogenic Escherichia coli virulence genes through control of the plasmid-encoded regulator, Per. Mol Microbiol. 2001;41:1133-50 pubmed
  4. Reed W, Schleif R. Hemiplegic mutations in AraC protein. J Mol Biol. 1999;294:417-25 pubmed
  5. Rhee S, Martin R, Rosner J, Davies D. A novel DNA-binding motif in MarA: the first structure for an AraC family transcriptional activator. Proc Natl Acad Sci U S A. 1998;95:10413-8 pubmed
    ..Extensive interactions between the recognition helices and the DNA major groove provide the sequence specificity...
  6. Bustos S, Schleif R. Functional domains of the AraC protein. Proc Natl Acad Sci U S A. 1993;90:5638-42 pubmed
    ..Dimerization was necessary for occupancy and activation of the wild-type AraC binding site. ..
  7. Martin K, Schleif R. Equilibrium DNA-binding of AraC protein. Compensation for displaced ions. J Mol Biol. 1987;195:741-4 pubmed
    ..As the protein binds the DNA, however, it undergoes a conformational change and binds about ten ions. Consequently, the net order of the reaction is reduced from 15th to about fourth order in salt concentration. ..
  8. Giangrossi M, Zattoni S, Tramonti A, De Biase D, Falconi M. Antagonistic role of H-NS and GadX in the regulation of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli. J Biol Chem. 2005;280:21498-505 pubmed
    ..Altogether, our results indicate that H-NS directly inhibits gadA and gadX transcription and, by controlling the intracellular level of the activator GadX, indirectly affects the expression of the whole gad system. ..
  9. Schleif R. AraC protein, regulation of the l-arabinose operon in Escherichia coli, and the light switch mechanism of AraC action. FEMS Microbiol Rev. 2010;34:779-96 pubmed publisher
    ..The sequence similarities among them are discussed in light of the known structure of the dimerization and DNA-binding domains of AraC. ..
  10. Tramonti A, De Canio M, De Biase D. GadX/GadW-dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY-gadW divergent promoters and identification of four novel 42 bp GadX/GadW-specific binding sites. Mol Microbiol. 2008;70:965-82 pubmed publisher
    ..The presence of five GadX/GadW-specific binding sites in the AFI suggests that GadX and GadW may act as H-NS counter-silencers. ..
  11. Lease R, Smith D, McDonough K, Belfort M. The small noncoding DsrA RNA is an acid resistance regulator in Escherichia coli. J Bacteriol. 2004;186:6179-85 pubmed
    ..Whether DsrA targets acid resistance genes directly by base pairing or indirectly via perturbation of RpoS and/or H-NS is not known, but in either event, our results suggest that DsrA RNA may enhance the virulence of pathogenic E. coli. ..
  12. Wu M, Schleif R. Mapping arm-DNA-binding domain interactions in AraC. J Mol Biol. 2001;307:1001-9 pubmed
    ..They form a contiguous trail on the DNA-distal face of the DNA-binding domain, and likely define the region where the N-terminal arm that extends from the N-terminal dimerization domain contacts the C-terminal DNA-binding domain. ..
  13. Harmer T, Wu M, Schleif R. The role of rigidity in DNA looping-unlooping by AraC. Proc Natl Acad Sci U S A. 2001;98:427-31 pubmed
    ..These results are consistent with the light switch mechanism for the action of AraC, refine the model, and extend the range of experimental tests to which it has been subjected. ..
  14. Tucker D, Tucker N, Ma Z, Foster J, Miranda R, Cohen P, et al. Genes of the GadX-GadW regulon in Escherichia coli. J Bacteriol. 2003;185:3190-201 pubmed
    ..Thus, E. coli colonization of the mouse does not appear to require glutamate-dependent acid resistance...
  15. Ma Z, Gong S, Richard H, Tucker D, Conway T, Foster J. GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12. Mol Microbiol. 2003;49:1309-20 pubmed
    ..The number of regulatory proteins (five), sigma factors (two) and regulatory feedback loops focused on gadA/BC expression make this one of the most intensively regulated systems in E. coli...
  16. Kwon H, Bennik M, Demple B, Ellenberger T. Crystal structure of the Escherichia coli Rob transcription factor in complex with DNA. Nat Struct Biol. 2000;7:424-30 pubmed
    ..These and other findings suggest that gene activation by AraC/XylS transcription factors might involve two alternative modes of binding to DNA in different promoter contexts. ..
  17. Johnson C, Schleif R. Cooperative action of the catabolite activator protein and AraC in vitro at the araFGH promoter. J Bacteriol. 2000;182:1995-2000 pubmed
    ..Finally, AraC protein also acts to prevent the improper binding of RNA polymerase at a pseudo promoter near the true p(FGH) promoter. ..
  18. Kolodrubetz D, Schleif R. Identification of araC protein and two-dimensional gels, its in vivo instability and normal level. J Mol Biol. 1981;149:133-9 pubmed
  19. Ghosh M, Schleif R. Biophysical evidence of arm-domain interactions in AraC. Anal Biochem. 2001;295:107-12 pubmed
    ..Alterations in the sequence of the arm which physiological experiments predict either to strengthen or weaken the arm produce the expected responses. ..
  20. Tobes R, Ramos J. AraC-XylS database: a family of positive transcriptional regulators in bacteria. Nucleic Acids Res. 2002;30:318-21 pubmed
    ..The AraC-XylS database is accessible on the World Wide Web at ..
  21. Seabold R, Schleif R. Apo-AraC actively seeks to loop. J Mol Biol. 1998;278:529-38 pubmed
    ..These affinities allowed accurate calculation of basal level and induced levels of expression from pBAD under a wide variety of natural and mutant conditions. The calculations independently predicted the looping preference of apo-AraC. ..
  22. Schleif R. AraC protein: a love-hate relationship. Bioessays. 2003;25:274-82 pubmed
  23. Weldon J, Rodgers M, Larkin C, Schleif R. Structure and properties of a truely apo form of AraC dimerization domain. Proteins. 2007;66:646-54 pubmed
    ..A slight change is observed in the relative orientation of monomers in the dimeric form of the domain upon the binding of arabinose but its significance cannot yet be assessed. ..
  24. Timmes A, Rodgers M, Schleif R. Biochemical and physiological properties of the DNA binding domain of AraC protein. J Mol Biol. 2004;340:731-8 pubmed
    ..A simple analysis relates the DNA binding affinities of monomers of DNA binding domain and normal dimeric AraC protein. ..
  25. Yang J, Tauschek M, Robins Browne R. Control of bacterial virulence by AraC-like regulators that respond to chemical signals. Trends Microbiol. 2011;19:128-35 pubmed publisher
  26. Martin K, Huo L, Schleif R. The DNA loop model for ara repression: AraC protein occupies the proposed loop sites in vivo and repression-negative mutations lie in these same sites. Proc Natl Acad Sci U S A. 1986;83:3654-8 pubmed
    ..Second, the mutational analysis presented here shows that the DNA components required for repression of araBAD are araI, araO2, and perhaps the araBAD operon RNA polymerase binding site. ..
  27. Egan S. Growing repertoire of AraC/XylS activators. J Bacteriol. 2002;184:5529-32 pubmed
  28. Hendrickson W, Schleif R. Regulation of the Escherichia coli L-arabinose operon studied by gel electrophoresis DNA binding assay. J Mol Biol. 1984;178:611-28 pubmed
    ..This result suggests that the inducing and repressing forms of araC protein displace a similar number of cations upon binding DNA. ..
  29. Guzman L, Belin D, Carson M, Beckwith J. Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol. 1995;177:4121-30 pubmed
    ..We have exploited the tight regulation of the PBAD promoter to study the phenotypes of null mutations of essential genes and explored the use of pBAD vectors as an expression system. ..
  30. Saviola B, Seabold R, Schleif R. DNA bending by AraC: a negative mutant. J Bacteriol. 1998;180:4227-32 pubmed
    ..Using the phase-sensitive DNA bending assay, we found that wild-type AraC bends DNA about 90 degrees whereas the mutant bends DNA by a smaller amount. ..
  31. Soisson S, MacDougall Shackleton B, Schleif R, Wolberger C. Structural basis for ligand-regulated oligomerization of AraC. Science. 1997;276:421-5 pubmed
    ..The ligand-gated oligomerization as seen in AraC provides the basis of a plausible mechanism for modulating the protein's DNA-looping properties. ..
  32. Rodgers M, Schleif R. Solution structure of the DNA binding domain of AraC protein. Proteins. 2009;77:202-8 pubmed publisher
    ..This solution structure is discussed in the context of extensive biochemical and physiological data on AraC and with respect to the DNA-bound structures of the MarA and Rob homologs. ..
  33. Johnson C, Schleif R. In vivo induction kinetics of the arabinose promoters in Escherichia coli. J Bacteriol. 1995;177:3438-42 pubmed
    ..5, 5, and 1, respectively. These results provide a basis for subsequent studies to determine the mechanism(s) by which AraC protein activates transcription from the different arabinose promoters. ..
  34. Gryczynski U, Schleif R. A portable allosteric mechanism. Proteins. 2004;57:9-11 pubmed
    ..Arabinose, which regulates the position of the arm in AraC protein now regulates the availability of the alpha-peptide to alpha-acceptor beta-galactosidase, thereby modulating its activity in response to arabinose. ..
  35. Ma Z, Richard H, Foster J. pH-Dependent modulation of cyclic AMP levels and GadW-dependent repression of RpoS affect synthesis of the GadX regulator and Escherichia coli acid resistance. J Bacteriol. 2003;185:6852-9 pubmed
    ..The presence of multiple pH control pathways governing expression of this acid resistance system is thought to reflect different environmental routes to a low pH...
  36. Dhiman A, Schleif R. Recognition of overlapping nucleotides by AraC and the sigma subunit of RNA polymerase. J Bacteriol. 2000;182:5076-81 pubmed
  37. Mahon V, Fagan R, Smith S. Snap denaturation reveals dimerization by AraC-like protein Rns. Biochimie. 2012;94:2058-61 pubmed publisher
    ..Furthermore, we demonstrate that Rns forms aggregates in vitro and describe a methodology to ameliorate aggregation thus permitting the analysis of Rns by cross-linking. ..
  38. Narasimhan G, Bu C, Gao Y, Wang X, Xu N, Mathee K. Mining protein sequences for motifs. J Comput Biol. 2002;9:707-20 pubmed
    ..The detection results for the two motifs compare favorably with existing programs. In addition, the GYM program provides a lot of useful information about a given protein sequence. ..
  39. Hirano T, Beck D, Wright C, Demuth D, Hackett M, Lamont R. Regulon controlled by the GppX hybrid two component system in Porphyromonas gingivalis. Mol Oral Microbiol. 2013;28:70-81 pubmed publisher
    ..Both the ?GppX mutant and a ?PGN_0151 mutant were deficient in monospecies biofilm formation, suggesting a role for the GppX-PGN_0151 regulon in colonization and survival of the organism...
  40. Plano G. Modulation of AraC family member activity by protein ligands. Mol Microbiol. 2004;54:287-90 pubmed
    ..The identification and characterization of several protein ligands that modify the activity of AraC family members in Pseudomonas aeruginosa and Salmonella enterica are discussed herein. ..
  41. Stoner C, Schleif R. Transcription start site and induction kinetics of the araC regulatory gene in Escherichia coli K-12. J Mol Biol. 1983;170:1049-53 pubmed
    ..Under all conditions tested, transcription initiated from the same nucleotide position at -148. ..
  42. Nishino K, Senda Y, Yamaguchi A. The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes. J Infect Chemother. 2008;14:23-9 pubmed publisher
    ..Our results indicate that the GadX regulator, in addition to its role in acid resistance, increases multidrug resistance in E. coli by activating the MdtEF multidrug efflux pump. ..
  43. Dunn T, Schleif R. Deletion analysis of the Escherichia coli ara PC and PBAD promoters. J Mol Biol. 1984;180:201-4 pubmed
    ..Similarly, deletions entering this site from the PBAD side reduced activity of the PC promoter. Cyclic AMP receptor protein bound at this site apparently functions to stimulate transcription of both flanking promoters. ..
  44. Coburn P, Baghdayan A, Dolan G, Shankar N. An AraC-type transcriptional regulator encoded on the Enterococcus faecalis pathogenicity island contributes to pathogenesis and intracellular macrophage survival. Infect Immun. 2008;76:5668-76 pubmed publisher
    ..These findings highlight the importance of PerA as a regulator of biofilm formation and survival within macrophages and is likely a regulator controlling determinants important to pathogenesis. ..
  45. Kosiba B, Schleif R. Arabinose-inducible promoter from Escherichia coli. Its cloning from chromosomal DNA, identification as the araFG promoter and sequence. J Mol Biol. 1982;156:53-66 pubmed
  46. BERRONDO M, Gray J, Schleif R. Computational predictions of the mutant behavior of AraC. J Mol Biol. 2010;398:462-70 pubmed publisher
    ..coli arm sequences do not fold to the E. coli arm structure. The high level of success shows that relatively "simple" computational methods can in some cases predict the behavior of mutant proteins with good reliability. ..
  47. Konopleva M, Watt J, Contractor R, Tsao T, Harris D, Estrov Z, et al. Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Res. 2008;68:3413-20 pubmed publisher
  48. Carra J, Schleif R. Formation of AraC-DNA sandwiches. Nucleic Acids Res. 1993;21:435-8 pubmed
    ..This behavior is consistent with the protein's ability to form DNA loops by binding to separated half sites in the absence of arabinose and its preference for binding to adjacent half-sites in the presence of arabinose. ..
  49. Ghosh M, Schleif R. Stabilizing C-terminal tails on AraC. Proteins. 2001;42:177-81 pubmed
    ..Hence, it appears that in the engineering of proteins, flexible tails may be freely added, with only the identity of the C-terminal amino acid being restricted. Proteins 2001;42:177-181. ..
  50. Lee S, Chou H, Pfleger B, Newman J, Yoshikuni Y, Keasling J. Directed evolution of AraC for improved compatibility of arabinose- and lactose-inducible promoters. Appl Environ Microbiol. 2007;73:5711-5 pubmed
    ..Detailed studies indicate that the AraC dimerization domain and C terminus are important for the increased sensitivity of AraC to arabinose. ..
  51. Yu Z, Bekker M, Tramonti A, Cook G, van Ulsen P, Scheffers D, et al. Activators of the glutamate-dependent acid resistance system alleviate deleterious effects of YidC depletion in Escherichia coli. J Bacteriol. 2011;193:1308-16 pubmed publisher
  52. Seedorff J, Schleif R. Active role of the interdomain linker of AraC. J Bacteriol. 2011;193:5737-46 pubmed publisher
    ..In summary, the linker does not simply function as a passive and flexible connector between the domains of AraC but, instead, is more directly involved in the protein's dimerization domain-DNA-binding domain interactions. ..
  53. Skredenske J, Koppolu V, Kolin A, Deng J, Kettle B, Taylor B, et al. Identification of a small-molecule inhibitor of bacterial AraC family activators. J Biomol Screen. 2013;18:588-98 pubmed publisher
    ..OSSL_051168 did not have a significant impact on DNA binding by the non-AraC family proteins CRP and LacI, suggesting that the inhibition is likely specific for RhaS, RhaR, and possibly additional AraC family activator proteins. ..