Two-component signal transduction systems are a primary means of regulating gene expression in bacteria. Recognizing the diversity of mechanisms associated with these systems is therefore critical to understanding the full signaling potential of bacterial cells. We have analyzed the behavior of two orphan, atypical response regulators that play key roles in controlling morphological differentiation in the filamentous bacteria Streptomyces-BldM and WhiI. We demonstrate that BldM activates its Group I target promoters as a homodimer, but that it subsequently activates its Group II target promoters by forming a functional heterodimer with WhiI. BldM-WhiI heterodimer formation thus represents an unusual mechanism for the coactivation of target genes and the integration of regulatory signals at promoters, enhancing the known repertoire of signaling capabilities associated with two-component systems.
Vyšlo v časopise: Response Regulator Heterodimer Formation Controls a Key Stage in S Development. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004554 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004554
1. CapraEJ, LaubMT (2012) Evolution of two-component signal transduction systems. Annu Rev Microbiol 66 : 325–347.
2. GaoR, StockAM (2009) Biological insights from structures of two-component proteins. Annu Rev Microbiol 63 : 133–154.
3. MitrophanovAY, GroismanEA (2008) Signal integration in bacterial two-component regulatory systems. Genes Dev 22 : 2601–2611.
4. Elliot MA, Buttner MJ, Nodwell JR (2008) Multicellular Development in Streptomyces. In: Whitworth DE, editor. Myxobacteria: Multicellularity and Differentiation. Washington D.C.: ASM Press. pp. 419–438.
5. FlärdhK, ButtnerMJ (2009) Streptomyces morphogenetics: dissecting differentiation in a filamentous bacterium. Nat Rev Microbiol 7 : 36–49.
6. McCormickJR, FlärdhK (2012) Signals and regulators that govern Streptomyces development. FEMS Microbiol Rev 36 : 206–231.
7. BourretRB (2010) Receiver domain structure and function in response regulator proteins. Curr Opin Microbiol 13 : 142–149.
8. HongE, LeeHM, KoH, KimDU, JeonBY, et al. (2007) Structure of an atypical orphan response regulator protein supports a new phosphorylation-independent regulatory mechanism. J Biol Chem 282 : 20667–20675.
9. FraserJS, MerlieJPJr, EcholsN, WeisfieldSR, MignotT, et al. (2007) An atypical receiver domain controls the dynamic polar localization of the Myxococcus xanthus social motility protein FrzS. Mol Microbiol 65 : 319–332.
10. WangL, TianX, WangJ, YangH, FanK, et al. (2009) Autoregulation of antibiotic biosynthesis by binding of the end product to an atypical response regulator. Proc Natl Acad Sci U S A 106 : 8617–8622.
11. HickeyJM, LovellS, BattaileKP, HuL, MiddaughCR, et al. (2011) The atypical response regulator protein ChxR has structural characteristics and dimer interface interactions that are unique within the OmpR/PhoB subfamily. J Biol Chem 286 : 32606–32616.
12. AínsaJA, ParryHD, ChaterKF (1999) A response regulator-like protein that functions at an intermediate stage of sporulation in Streptomyces coelicolor A3(2). Mol Microbiol 34 : 607–619.
13. TianY, FowlerK, FindlayK, TanH, ChaterKF (2007) An unusual response regulator influences sporulation at early and late stages in Streptomyces coelicolor. J Bacteriol 189 : 2873–2885.
14. MolleV, ButtnerMJ (2000) Different alleles of the response regulator gene bldM arrest Streptomyces coelicolor development at distinct stages. Mol Microbiol 36 : 1265–1278.
15. BibbMJ, MolleV, ButtnerMJ (2000) σBldN, an extracytoplasmic function RNA polymerase sigma factor required for aerial mycelium formation in Streptomyces coelicolor A3(2). J Bacteriol 182 : 4606–4616.
16. BibbMJ, DomonkosÁ, ChandraG, ButtnerMJ (2012) Expression of the chaplin and rodlin hydrophobic sheath proteins in Streptomyces venezuelae is controlled by σBldN and a cognate anti-sigma factor, RsbN. Mol Microbiol 84 : 1033–1049.
17. ElliotMA, KaroonuthaisiriN, HuangJ, BibbMJ, CohenSN, et al. (2003) The chaplins: a family of hydrophobic cell-surface proteins involved in aerial mycelium formation in Streptomyces coelicolor. Genes Dev 17 : 1727–1740.
18. ClaessenD, RinkR, de JongW, SiebringJ, de VreugdP, et al. (2003) A novel class of secreted hydrophobic proteins is involved in aerial hyphae formation in Streptomyces coelicolor by forming amyloid-like fibrils. Genes Dev 17 : 1714–1726.
19. ClaessenD, StokroosI, DeelstraHJ, PenningaNA, BormannC, et al. (2004) The formation of the rodlet layer of streptomycetes is the result of the interplay between rodlins and chaplins. Mol Microbiol 53 : 433–443.
20. BushMJ, BibbMJ, ChandraG, FindlayKC, ButtnerMJ (2013) Genes required for aerial growth, cell division, and chromosome segregation are targets of WhiA before sporulation in Streptomyces venezuelae. MBio 4: e00684–13.
21. Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. In: Proceedings of the Second International Conference on Intelligent Systems for Molecular Biology. Menlo Park: AAAI Press. pp 28–36.
22. GregoryMA, TillR, SmithMCM (2003) Integration site for Streptomyces phage ΦBT1 and development of site-specific integrating vectors. J Bacteriol 185 : 5320–5323.
23. KarimovaG, PidouxJ, UllmannA, LadantD (1998) A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci USA 95 : 5752–5756.
24. NashHA, RobertsonCA, FlammE, WeisbergRA, MillerHI (1987) Overproduction of Escherichia coli integration host factor, a protein with nonidentical subunits. J Bacteriol 169 : 4124–4127.
25. den HengstCD, TranNT, BibbMJ, ChandraG, LeskiwBK, et al. (2010) Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth. Mol Microbiol 78 : 361–379.
26. WillemseJ, BorstJW, de WaalE, BisselingT, van WezelGP (2011) Positive control of cell division: FtsZ is recruited by SsgB during sporulation of Streptomyces. Genes Dev 25 : 89–99.
27. van WezelGP, van der MeulenJ, KawamotoS, LuitenRG, KoertenHK, et al. (2000) ssgA is essential for sporulation of Streptomyces coelicolor A3(2) and affects hyphal development by stimulating septum formation. J Bacteriol 182 : 5653–5662.
28. KeijserBJ, NoensEE, KraalB, KoertenHK, van WezelGP (2003) The Streptomyces coelicolor ssgB gene is required for early stages of sporulation. FEMS Microbiol Lett 225 : 59–67.
29. TraagBA, KelemenGH, van WezelGP (2004) Transcription of the sporulation gene ssgA is activated by the IclR-type regulator SsgR in a whi-independent manner in Streptomyces coelicolor A3(2). Mol Microbiol 53 : 985–1000.
30. FlärdhK, FindlayKC, ChaterKF (1999) Association of early sporulation genes with suggested developmental decision points in Streptomyces coelicolor A3(2). Microbiology 145 : 2229–2243.
31. JakimowiczP, CheesmanMR, BishaiWR, ChaterKF, ThomsonAJ, et al. (2005) Evidence that the Streptomyces developmental protein WhiD, a member of the WhiB family, binds a [4Fe-4S] cluster. J Biol Chem 280 : 8309–8315.
32. SinghA, GuidryL, NarasimhuluKV, MaiD, TrombleyJ, et al. (2007) Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival. Proc Natl Acad Sci U S A 104 : 11562–11567.
33. SinghA, CrossmanDK, MaiD, GuidryL, VoskuilMI, et al. (2009) Mycobacterium tuberculosis WhiB3 maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response. PLoS Pathog 5: e1000545.
34. CrackJC, den HengstCD, JakimowiczP, SubramanianS, JohnsonMK, et al. (2009) Characterization of [4Fe-4S]-containing and cluster-free forms of Streptomyces WhiD. Biochemistry 48 : 12252–12264.
35. CrackJC, SmithLJ, StapletonMR, PeckJ, WatmoughNJ, et al. (2011) Mechanistic insight into the nitrosylation of the [4Fe-4S] cluster of WhiB-like proteins. J Am Chem Soc 133 : 1112–1121.
36. den HengstCD, ButtnerMJ (2008) Redox control in actinobacteria. Biochem Biophys Acta 1780 : 1201–1216.
37. SmithL, StapletonMR, FullstoneGJ, CrackJC, ThomsonAJ, et al. (2010) Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster. Biochem J 432 : 417–427.
38. RybnikerJ, NowagA, van GumpelE, NissenN, RobinsonN, et al. (2010) Insights into the function of the WhiB-like protein of mycobacteriophage TM4 - a transcriptional inhibitor of WhiB2. Mol Microbiol 77 : 642–657.
39. AusmeesN, WahlstedtH, BagchiS, ElliotMA, ButtnerMJ, et al. (2007) SmeA, a small membrane protein with multiple functions in Streptomyces sporulation including targeting of a SpoIIIE/FtsK-like protein to cell division septa. Mol Microbiol 65 : 1458–1473.
40. DavisNK, ChaterKF (1990) Spore colour in Streptomyces coelicolor A3(2) involves the developmentally regulated synthesis of a compound biosynthetically related to polyketide antibiotics. Mol Microbiol 4 : 1679–1691.
41. YuT-W, HopwoodDA (1995) Ectopic expression of the Streptomyces coelicolor whiE genes for polyketide spore pigment synthesis and their interaction with the act genes for actinorhodin biosynthesis. Microbiology 141 : 2779–2791.
42. KelemenGH, BrianP, FlärdhK, ChamberlinL, ChaterKF, et al. (1998) Developmental regulation of transcription of whiE, a locus specifying the polyketide spore pigment in Streptomyces coelicolor A3(2). J Bacteriol 180 : 2515–2521.
43. ZhangG, TianY, HuK, ZhuY, ChaterKF, et al. (2012) Importance and regulation of inositol biosynthesis during growth and differentiation of Streptomyces. Mol Microbiol 83 : 1178–1194.
44. ReményiA, SchölerHR, WilmannsM (2004) Combinatorial control of gene expression. Nat Struct Mol Biol 11 : 812–815.
45. MajdalaniN, GottesmanS (2005) The Rcs phosphorelay: a complex signal transduction system. Annu Rev Microbiol 59 : 379–405.
46. MajdalaniN, GottesmanS (2007) Genetic dissection of signaling through the Rcs phosphorelay. Methods Enzymol 423 : 349–362.
47. VenkateshGR, Kembou KoungniFC, PauknerA, StratmannT, BlissenbachB, et al. (2010) BglJ-RcsB heterodimers relieve repression of the Escherichia coli bgl operon by H-NS. J Bacteriol 192 : 6456–6464.
48. Castanié-CornetMP, CamK, BastiatB, CrosA, BordesP, et al. (2010) Acid stress response in Escherichia coli: mechanism of regulation of gadA transcription by RcsB and GadE. Nucleic Acids Res 38 : 3546–3554.
49. GaoR, TaoY, StockAM (2008) System-level mapping of Escherichia coli response regulator dimerization with FRET hybrids. Mol Microbiol 69 : 1358–1372.
50. LeeDJ, MinchinSD, BusbySJ (2012) Activating transcription in bacteria. Annu Rev Microbiol 66 : 125–152.
51. BrowningDF, BusbySJ (2004) The regulation of bacterial transcription initiation. Nat Rev Microbiol 2 : 57–65.
52. WadeJT, BelyaevaTA, HydeEI, BusbySJ (2001) A simple mechanism for co-dependence on two activators at an Escherichia coli promoter. EMBO J 20 : 7160–7167.
53. RichetE, Vidal-IngigliardiD, RaibaudO (1991) A new mechanism for coactivation of transcription initiation: repositioning of an activator triggered by the binding of a second activator. Cell 66 : 1185–1195.
54. Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical Streptomyces Genetics. The John Innes Foundation. Norwich, United Kingdom.
55. GustB, ChallisGL, FowlerK, KieserT, ChaterKF (2003) PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc Natl Acad Sci U S A 100 : 1541–1546.
56. Cairns J, Spyrou C, Stark R, Smith ML, Lynch AG, et al. 2011. BayesPeak—an R package for analysing ChIP-seq data. Bioinformatics 27 : 713–714.
57. SaeedAI, BhagabatiNK, BraistedJC, LiangW, SharovV, et al. (2006) TM4 microarray software suite. Methods Enzymol 411 : 134–193.
58. BreitlingR, ArmengaudP, AmtmannA, HerzykP (2004) Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 573 : 83–92.
59. AllenbyNE, LaingE, BuccaG, KierzekAM, SmithCP (2012) Diverse control of metabolism and other cellular processes in Streptomyces coelicolor by the PhoP transcription factor: genome-wide identification of in vivo targets. Nucleic Acids Res 40 : 9543–9556.
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