Information de reference pour ce titreAccession Number: | 00006178-201240210-00045.
|
Author: | Meinhardt, Sarah 1; Manley, Michael W. Jr 1; Becker, Nicole A. 2; Hessman, Jacob A. 1; Maher, L. James III 2; Swint-Kruse, Liskin 1,*
|
Institution: | (1)Department of Biochemistry and Molecular Biology, The University of Kansas Medical Center, Kansas City, KS 66160 and (2)Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, SW, Rochester, MN 55905, USA
|
Title: | Novel insights from hybrid LacI/GalR proteins: family-wide functional attributes and biologically significant variation in transcription repression.[Miscellaneous Article]
|
Source: | Nucleic Acids Research. 40(21):11139-11154, November 2012.
|
Abstract: | LacI/GalR transcription regulators have extensive, non-conserved interfaces between their regulatory domains and the 18 amino acids that serve as 'linkers' to their DNA-binding domains. These non-conserved interfaces might contribute to functional differences between paralogs. Previously, two chimeras created by domain recombination displayed novel functional properties. Here, we present a synthetic protein family, which was created by joining the LacI DNA-binding domain/linker to seven additional regulatory domains. Despite 'mismatched' interfaces, chimeras maintained allosteric response to their cognate effectors. Therefore, allostery in many LacI/GalR proteins does not require interfaces with precisely matched interactions. Nevertheless, the chimeric interfaces were not silent to mutagenesis, and preliminary comparisons suggest that the chimeras provide an ideal context for systematically exploring functional contributions of non-conserved positions. DNA looping experiments revealed higher order (dimer-dimer) oligomerization in several chimeras, which might be possible for the natural paralogs. Finally, the biological significance of repression differences was determined by measuring bacterial growth rates on lactose minimal media. Unexpectedly, moderate and strong repressors showed an apparent induction phase, even though inducers were not provided; therefore, an unknown mechanism might contribute to regulation of the lac operon. Nevertheless, altered growth correlated with altered repression, which indicates that observed functional modifications are significant.
(C) Copyright Oxford University Press 2012.
|
References: | 1. Bashton M, Chothia C. The generation of new protein functions by the combination of domains Structure. 2007;15:85-99
2. Lim WA. The modular logic of signaling proteins: building allosteric switches from simple binding domains Curr. Opin. Struct. Biol.. 2002;12:61-68
3. Guntas G, Mitchell SF, Ostermeier M. A molecular switch created by in vitro recombination of nonhomologous genes Chem. Biol.. 2004;11:1483-1487
4. Wong-Deyrup SW, Prasannan C, Dupureur CM, Franklin SJ. DNA targeting and cleavage by an engineered metalloprotein dimer J. Biol. Inorg. Chem. 2011;17:387-398
5. Goyal R, Salahudeen AA, Jansen M. Engineering a prokaryotic Cys-loop receptor with a third functional domain J. Biol. Chem.. 2011;286:34635-34642
6. Swint-Kruse L, Matthews KS. Allostery in the LacI/GalR family: variations on a theme Curr. Opin. Microbiol.. 2009;12:129-137
7. Schumacher MA, Glasfeld A, Zalkin H, Brennan RG. The X-ray structure of the PurR-guanine-purF operator complex reveals the contributions of complementary electrostatic surfaces and a water-mediated hydrogen bond to corepressor specificity and binding affinity J. Biol. Chem.. 1997;272:22648-22653
8. Bell CE, Lewis M. A closer view of the conformation of the Lac repressor bound to operator Nat. Struct. Biol.. 2000;7:209-214
9. Schumacher MA, Allen GS, Diel M, Seidel G, Hillen W, Brennan RG. Structural basis for allosteric control of the transcription regulator CcpA by the phosphoprotein HPr-Ser46-P Cell. 2004;118:731-741
10. Swint-Kruse L, Larson C, Pettitt BM, Matthews KS. Fine-tuning function: correlation of hinge domain interactions with functional distinctions between LacI and PurR Protein Sci.. 2002;11:778-794
11. Tungtur S, Parente DJ, Swint-Kruse L. Functionally important positions can comprise the majority of a protein's architecture Prot. Struct. Func. Bioinf.. 2011;79:1589-1608
12. Tungtur S, Egan SM, Swint-Kruse L. Functional consequences of exchanging domains between LacI and PurR are mediated by the intervening linker sequence Proteins. 2007;68:375-388
13. Meinhardt S, Swint-Kruse L. Experimental identification of specificity determinants in the domain linker of a LacI/GalR protein: bioinformatics-based predictions generate true positives and false negatives Proteins. 2008;73:941-957
14. Tungtur S, Meinhardt S, Swint-Kruse L. Comparing the functional roles of nonconserved sequence positions in homologous transcription repressors: implications for sequence/function analyses J. Mol. Biol.. 2010;395:785-802
15. Tungtur S, Skinner H, Zhan H, Swint-Kruse L, Beckett D. In vivo tests of thermodynamic models of transcription repressor function Biophys. Chem.. 2011;159:142-151
16. Zhan H, Taraban M, Trewhella J, Swint-Kruse L. Subdividing repressor function: DNA binding affinity, selectivity, and allostery can be altered by amino acid substitution of nonconserved residues in a LacI/GalR homologue Biochemistry. 2008;47:8058-8069
17. Zhan H, Swint-Kruse L, Matthews KS. Extrinsic interactions dominate helical propensity in coupled binding and folding of the lactose repressor protein hinge helix Biochemistry. 2006;45:5896-5906
18. Jobe A, Bourgeois S. lac Repressor-operator interaction. VI. The natural inducer of the lac operon J. Mol. Biol.. 1972;69:397-408
19. Neidhardt FC, Bloch PL, Smith DF. Culture medium for enterobacteria J. Bacteriol.. 1974;119:736-747
20. Bhende PM, Egan SM. Amino acid-DNA contacts by RhaS: an AraC family transcription activator J. Bacteriol.. 1999;181:5185-5192
21. Swint-Kruse L, Zhan H, Fairbanks BM, Maheshwari A, Matthews KS. Perturbation from a distance: mutations that alter LacI function through long-range effects Biochemistry. 2003;42:14004-14016
22. Geanacopoulos M, Adhya S. Genetic analysis of GalR tetramerization in DNA looping during repressosome assembly J. Biol. Chem.. 2002;277:33148-33152
23. Chen J, Matthews KS. Subunit dissociation affects DNA binding in a dimeric lac repressor produced by C-terminal deletion Biochemistry. 1994;33:8728-8735
24. Suckow J, Markiewicz P, Kleina LG, Miller J, Kisters-Woike B, Muller-Hill B. Genetic studies of the Lac repressor. XV: 4000 single amino acid substitutions and analysis of the resulting phenotypes on the basis of the protein structure J. Mol. Biol.. 1996;261:509-523
25. Falcon CM, Matthews KS. Engineered disulfide linking the hinge regions within lactose repressor dimer increases operator affinity, decreases sequence selectivity, and alters allostery Biochemistry. 2001;40:15650-15659
26. Swint-Kruse L, Zhan H, Matthews KS. Integrated insights from simulation, experiment, and mutational analysis yield new details of LacI function Biochemistry. 2005;44:11201-11213
27. Oehler S, Eismann ER, Kramer H, Muller-Hill B. The three operators of the lac operon cooperate in repression EMBO J.. 1990;9:973-979
28. Sadler JR, Sasmor H, Betz JL. A perfectly symmetric lac operator binds the lac repressor very tightly Proc. Natl Acad. Sci. USA. 1983;80:6785-6789
29. Miller JH A Short Course in Bacterial Genetics: A Laboratory Handbook for Escherichia Coli and Related Bacteria. 1992 Plainview, NY Cold Spring Harbor Laboratory Press
30. Riggs AD, Newby RF, Bourgeois S. lac repressor-operator interaction. II. Effect of galactosides and other ligands J. Mol. Biol.. 1970;51:303-314
31. Manly SP, Matthews KS. Activity changes in lac repressor with cysteine oxidation J. Biol. Chem.. 1979;254:3341-3347
32. Becker NA, Kahn JD, Maher LJ 3rd. Bacterial repression loops require enhanced DNA flexibility J. Mol. Biol.. 2005;349:716-730
33. Chen J, Matthews KS. T41 mutation in lac repressor is Tyr282-Asp Gene. 1992;111:145-146
34. Chakerian AE, Matthews KS. Characterization of mutations in oligomerization domain of Lac repressor protein J. Biol. Chem.. 1991;266:22206-22214
35. Schmitz A, Schmeissner U, Miller JH. Mutations affecting the quaternary structure of the lac repressor J. Biol. Chem.. 1976;251:3359-3366
36. Whipple FW. Genetic analysis of prokaryotic and eukaryotic DNA-binding proteins in Escherichia coli Nucleic Acids Res.. 1998;26:3700-3706
37. Weickert MJ, Adhya S. A family of bacterial regulators homologous to Gal and Lac repressors J. Biol. Chem.. 1992;267:15869-15874
38. Choi KY, Zalkin H. Structural characterization and corepressor binding of the Escherichia coli purine repressor J. Bacteriol.. 1992;174:6207-6214
39. Meng LM, Nygaard P. Identification of hypoxanthine and guanine as the co-repressors for the purine regulon genes of Escherichia coli Mol. Microbiol.. 1990;4:2187-2192
40. Gavigan SA, Nguyen T, Nguyen N, Senear DF. Role of multiple CytR binding sites on cooperativity, competition, and induction at the Escherichia coli udp promoter J. Biol. Chem.. 1999;274:16010-16019
41. Pedersen H, Sogaard-Andersen L, Holst B, Valentin-Hansen P. Heterologous cooperativity in Escherichia coli. The CytR repressor both contacts DNA and the cAMP receptor protein when binding to the deoP2 promoter J. Biol. Chem.. 1991;266:17804-17808
42. Tretyachenko-Ladokhina V, Cocco MJ, Senear DF. Flexibility and adaptability in binding of E. coli cytidine repressor to different operators suggests a role in differential gene regulation J. Mol. Biol.. 2006;362:271-286
43. Kallipolitis BH, Norregaard-Madsen M, Valentin-Hansen P. Protein-protein communication: structural model of the repression complex formed by CytR and the global regulator CRP Cell. 1997;89:1101-1109
44. Hall BG, Xu L. Nucleotide sequence, function, activation, and evolution of the cryptic asc operon of Escherichia coli K12 Mol. Biol. Evol.. 1992;9:688-706
45. Weickert MJ, Adhya S. Isorepressor of the gal regulon in Escherichia coli J. Mol. Biol.. 1992;226:69-83
46. Geanacopoulos M, Adhya S. Functional characterization of roles of GalR and GalS as regulators of the gal regulon J. Bacteriol.. 1997;179:228-234
47. Mossing MC, Record MT Jr. Upstream operators enhance repression of the lac promoter Science. 1986;233:889-892
48. Semsey S, Virnik K, Adhya S. Three-stage regulation of the Amphibolic gal operon: from repressosome to GalR-free DNA J. Mol. Biol.. 2006;358:355-363
49. Kramer H, Niemoller M, Amouyal M, Revet B, von Wilcken-Bergmann B, Muller-Hill B. lac repressor forms loops with linear DNA carrying two suitably spaced lac operators EMBO J.. 1987;6:1481-1491
50. Muller J, Oehler S, Muller-Hill B. Repression of lac promoter as a function of distance, phase, and quality of an auxilary lac operator J. Mol. Biol.. 1996;257:21-29
51. Matthews KS. DNA looping Microbiol. Rev.. 1992;56:123-136
52. Eismann E, von Wilcken-Bergmann B, Muller-Hill B. Specific destruction of the second lac operator decreases repression of the lac operon in Escherichia coli fivefold J. Mol. Biol.. 1987;195:949-952
53. Muller J, Barker A, Oehler S, Muller-Hill B. Dimeric lac repressors exhibit phase-dependent co-operativity J. Mol. Biol.. 1998;284:851-857
54. Poelwijk FJ, Heyning PD, de Vos MG, Kiviet DJ, Tans SJ. Optimality and evolution of transcriptionally regulated gene expression BMC Syst. Biol.. 2011;5:128
55. Monod J. The phenomenon of enzymatic adaptation and its bearings on problems of genetics and cellular differentiation Growth. 1947;11:223-289
56. Wilson CJ, Zhan H, Swint-Kruse L, Matthews KS. The lactose repressor system: paradigms for regulation, allosteric behavior and protein folding Cell Mol. Life Sci.. 2007;64:3-16
57. Mowbray SL, Bjorkman AJ. Conformational changes of ribose-binding protein and two related repressors are tailored to fit the functional need J. Mol. Biol.. 1999;294:487-499
58. Gama-Castro S, Salgado H, Peralta-Gil M, Santos-Zavaleta A, Muniz-Rascado L, Solano-Lira H, Jimenez-Jacinto V, Weiss V, Garcia-Sotelo JS, Lopez-Fuentes A, et al. RegulonDB version 7.0: transcriptional regulation of Escherichia coli K-12 integrated within genetic sensory response units (Gensor Units) Nucleic Acids Res.. 2011;39:D98-D105
59. Shimada T, Yamamoto K, Ishihama A. Novel members of the Cra regulon involved in carbon metabolism in Escherichia coli J. Bacteriol.. 2011;193:649-659
60. Cho BK, Federowicz SA, Embree M, Park YS, Kim D, Palsson BO. The PurR regulon in Escherichia coli K-12 MG1655 Nucleic Acids Res.. 2011;39:6456-6464
61. Ishida Y, Kori A, Ishihama A. Participation of regulator AscG of the beta-glucoside utilization operon in regulation of the propionate catabolism operon J. Bacteriol.. 2009;191:6136-6144
62. Pei J, Cai W, Kinch LN, Grishin NV. Prediction of functional specificity determinants from protein sequences using log-likelihood ratios Bioinformatics. 2006;22:164-171
63. Kalinina OV, Novichkov PS, Mironov AA, Gelfand MS, Rakhmaninova AB. SDPpred: a tool for prediction of amino acid residues that determine differences in functional specificity of homologous proteins Nucleic Acids Res.. 2004;32:424-428
64. Ye K, Feenstra AK, Heringa J, Ijzerman AP, Marchiori E. Multi-RELIEF: a method to recognize specificity determining residues from multiple sequence alignments using a machine-learning approach for feature weighting Bioinformatics. 2008;24:18-25
65. Ye K, Vriend G, Ijzerman AP. Tracing evolutionary pressure Bioinformatics. 2008;24:908-915
66. Binkley J, Karra K, Kirby A, Hosobuchi M, Stone EA, Sidow A. ProPhylER: A curated online resource for protein function and structure based on evolutionary constraint analyses Genome Res.. 2010;20:142-154
67. Cai ZH, Tsung EF, Marinescu VD, Ramoni MF, Riva A, Kohane IS. Bayesian approach to discovering pathogenic SNPs in conserved protein domains Hum. Mutat.. 2004;24:178-184
68. Chasman D, Adams RM. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation J. Mol. Biol.. 2001;307:683-706
69. Chen HL, Zhou HX. Prediction of solvent accessibility and sites of deleterious mutations from protein sequence Nucleic Acids Res.. 2005;33:3193-3199
70. Chiu HC, Chang CA, Hu YJ. Prediction of orthologous relationship by functionally important sites Comput. Meth. Programs Biomed.. 2005;78:209-222
71. Jiang R, Yang H, Sun F, Chen T. Searching for interpretable rules for disease mutations: a simulated annealing bump hunting strategy BMC Bioinformatics. 2006;7:417
72. Krishnan VG, Westhead DR. A comparative study of machine-learning methods to predict the effects of single nucleotide polymorphisms on protein function Bioinformatics. 2003;19:2199-2209
73. Lau AY, Chasman DI. Functional classification of proteins and protein variants Proc. Natl Acad. Sci. USA. 2004;101:6576-6581
74. Lee W, Zhang Y, Mukhyala K, Lazarus RA, Zhang Z. Bi-directional SIFT predicts a subset of activating mutations PloS One. 2009;4:e8311
75. Marini NJ, Thomas PD, Rine J. The use of orthologous sequences to predict the impact of amino acid substitutions on protein function PloS Genet. 2010;6:e1000968
76. Needham CJ, Bradford JR, Bulpitt AJ, Care MA, Westhead DR. Predicting the effect of missense mutations on protein function: analysis with Bayesian networks BMC Bioinformatics. 2006;7:405
77. Ng PC, Henikoff S. Predicting deleterious amino acid substitutions Genome Res.. 2001;11:863-874
78. De Crombrugghe B, Chen B, Anderson W, Nissley P, Gottesman M, Pastan I, Perlman R. Lac DNA, RNA polymerase and cyclic AMP receptor protein, cyclic AMP, lac repressor and inducer are the essential elements for controlled lac transcription Nat. New Biol.. 1971;231:139-142
79. Schlax PJ, Capp MW, Record TM Jr. Inhibition of transcription initiation by IacRepressor J. Mol. Biol.. 1995;245:331-350
80. Sanchez A, Osborne ML, Friedman LJ, Kondev J, Gelles J. Mechanism of transcriptional repression at a bacterial promoter by analysis of single molecules EMBO J.. 2011;30:3940-3946
81. Jones DH. PCR mutagenesis and recombination in vivo PCR Methods Appl.. 1994;3:S141-S148
82. Majumdar A, Rudikoff S, Adhya S. Purification and properties of Gal repressor:pL-galR fusion in pKC31 plasmid vector J. Biol. Chem.. 1987;262:2326-2331
83. Saier MH Jr, Ramseier TM. The catabolite repressor/activator (Cra) protein of enteric bacteria J. Bacteriol.. 1996;178:3411-3417
84. Ramseier TM, Negre D, Cortay JC, Scarabel M, Cozzone AJ, Saier MH Jr. In vitro binding of the pleiotropic transcriptional regulatory protein, FruR, to the fru, pps, ace, pts and icd operons of Escherichia coli and Salmonella typhimurium J. Mol. Biol.. 1993;234:28-44
85. Horlacher R, Boos W. Characterization of TreR, the major regulator of the Escherichia coli trehalose system J. Biol. Chem.. 1997;272:13026-13032
86. Mauzy CA, Hermodson MA. Structural homology between rbs repressor and ribose binding protein implies functional similarity Protein Sci.. 1992;1:843-849
87. Barbier CS, Short SA, Senear DF. Allosteric mechanism of induction of CytR-regulated gene expression. Cytr repressor-cytidine interaction J. Biol. Chem.. 1997;272:16962-16971
88. Spiridonov NA, Wilson DB. Characterization and cloning of celR, a transcriptional regulator of cellulase genes from Thermomonospora fusca J. Biol. Chem.. 1999;274:13127-13132
89. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera-a visualization system for exploratory research and analysis J. Comput. Chem.. 2004;25:1605-1612
90. Alberti S, Oehler S, von Wilcken-Bergmann B, Kramer H, Muller-Hill B. Dimer-to-tetramer assembly of lac repressor involves a leucine heptad repeat New Biologist. 1991;3:57-62
91. Taraban M, Zhan H, Whitten AE, Langley DB, Matthews KS, Swint-Kruse L, Trewhella J. Ligand-induced conformational changes and conformational dynamics in the solution structure of the lactose repressor protein J. Mol. Biol.. 2008;376:466-481
|
Language: | English.
|
Document Type: | Synthetic Biology and Chemistry.
|
Journal Subset: | Life & Biomedical Sciences.
|
ISSN: | 0305-1048
|
NLM Journal Code: | o8l, 0411011
|
DOI Number: | https://dx.doi.org/10.1093/nar/g...- ouverture dans une nouvelle fenêtre
|
Annotation(s) | |
|
|