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MetJ DNA-binding transcriptional repressor

Synonyms: MetJ-S-adenosyl-L-methionine, MetJ-MTA, MetJ-adenine, MetJ
Summary:
MetJ represses the expression of genes involved in biosynthesis and transport of methionine [2, 9]. MetJ belongs to the ribbon-helix-helix family of regulatory proteins. The typical motif of members of this family, the ribbon-helix-helix motif for DNA binding, has been observed in the crystalline structure of MetJ [10]. This motif is composed of a two-stranded antiparallel β-ribbon that lies along the DNA major groove, two outer α-helices that interact with adjacent proteins along the DNA, and two inner β-helices that form the subunit interface [10]. MetJ as a homodimer [10, 11] recognizes and binds to an 8-bp DNA sequence called the met-box, which varies around a perfect palindromic consensus sequence [12, 13, 14]. MetJ finds its target sites rapidly by facilitated diffusion [15].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MetJ Non-Functional   Apo nd nd
MetJ-S-adenosyl-L-methionine Functional Allosteric Holo nd nd
MetJ-MTA Non-Functional   nd nd
MetJ-adenine Non-Functional   nd nd
Evolutionary Family: MetJ
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: metJ
  Genome position: 4128078-4128395
  Length: 318 bp / 105 aa
Operon name: metJ
TU(s) encoding the TF:
Transcription unit        Promoter
metJ
metJp1
metJ
metJp2
metJ
metJp3


Regulon       
Regulated gene(s) ahpC, ahpF, folE, metA, metB, metC, metE, metF, metI, metK, metL, metN, metQ, metR, yeiB
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
methionine (5)
detoxification (2)
folic acid (1)
amino acids (1)
threonine catabolism (1)
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Regulated operon(s) ahpCF, folE-yeiB, metA, metBL, metC, metE, metF, metK, metNIQ, metR
First gene in the operon(s) ahpC, folE, metA, metB, metC, metE, metF, metK, metN, metR
Simple and complex regulons CRP,MetJ
HypT,MetJ
HypT,MetJ,PhoP
MetJ
MetJ,MetR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MetJ,-](12)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  MetJ-S-adenosyl-L-methionine repressor ahpCp1 Sigma70 17.5 -7.5 ahpC, ahpF
catcgaaaacACGGAGGAAGTATAGAtgtccttgat
638930 638945 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor ahpCp1 Sigma70 27.5 3.5 ahpC, ahpF
acggaggaagTATAGATGTCCTTGATtaacaccaaa
638940 638955 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 25.5 -171.5 folE, yeiB
tttcacttccGTATTTGCATAACGATgttttaacat
2243816 2243831 [GEA], [AIBSCS], [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 33.5 -163.5 folE, yeiB
ccgtatttgcATAACGATGTTTTAACatctgctgat
2243808 2243823 [GEA], [AIBSCS], [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 41.5 -155.5 folE, yeiB
gcataacgatGTTTTAACATCTGCTGatgaaaggca
2243800 2243815 [GEA], [AIBSCS], [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 49.5 -147.5 folE, yeiB
atgttttaacATCTGCTGATGAAAGGcagcggcaat
2243792 2243807 [GEA], [AIBSCS], [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor metAp1 Sigma32 4.5 -43.5 metA
ggttatcttcAGCTATCTGGATGTCTaaacgtataa
4214229 4214244 [GEA], [AIBSCS], [BCE], [BPP] [1], [2]
  MetJ-S-adenosyl-L-methionine repressor metAp1 Sigma32 20.5 -27.5 metA
ctggatgtctAAACGTATAAGCGTATgtagtgaggt
4214245 4214260 [GEA], [AIBSCS], [BCE], [BPP] [1], [2]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -56.5 -92.5 metB, metL
tcaatctataCGCAAAGAAGTTTAGAtgtccagatg
4128572 4128587 [GEA], [AIBSCS] [1], [2], [3]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -48.5 -84.5 metB, metL
tacgcaaagaAGTTTAGATGTCCAGAtgtattgacg
4128580 4128595 [GEA], [AIBSCS] [1], [2], [3]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -46.5 -82.5 metB, metL
cgcaaagaagTTTAGATGTCCAGATGtattgacgtc
4128582 4128597 [GEA], [AIBSCS] [1], [2], [3]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -40.5 -76.5 metB, metL
gaagtttagaTGTCCAGATGTATTGAcgtccattaa
4128588 4128603 [GEA], [AIBSCS] [1], [2], [3]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -38.5 -74.5 metB, metL
agtttagatgTCCAGATGTATTGACGtccattaaca
4128590 4128605 [GEA], [AIBSCS] [1], [2], [3]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -30.5 -66.5 metB, metL
tgtccagatgTATTGACGTCCATTAAcacaatgttt
4128598 4128613 [GEA], [AIBSCS] [1], [2], [3]
  MetJ-S-adenosyl-L-methionine repressor metCp Sigma70 nd nd metC nd nd [BPP] [4], [5]
  MetJ-S-adenosyl-L-methionine repressor metEp nd 1.5 -168.5 metE
aaccgccaatTATGGATGTGTAAACAtctggacggc
4012877 4012892 [BPP] [6]
  MetJ-S-adenosyl-L-methionine repressor metEp nd 116.5 -53.5 metE
ggatgaataaACTTGCCGCCTTCCCTaaattcaaaa
4012992 4013007 [BPP] [6]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 -8.5 -78.5 metF
gcccttcggcTTTTCCTTCATCTTTAcatctggacg
4132530 4132545 [BCE], [SM]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 2.0 -69.0 metF
cttttccttcATCTTTACATCTGGACgtctaaacgg
4132539 4132554 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 4.5 -66.5 metF
ttccttcatcTTTACATCTGGACGTCtaaacggata
4132542 4132557 [BCE], [SM]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 7.5 -63.5 metF
cttcatctttACATCTGGACGTCTAAacggatagat
4132545 4132560 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 9.5 -61.5 metF
tcatctttacATCTGGACGTCTAAACggatagatgt
4132547 4132562 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 17.5 -53.5 metF
acatctggacGTCTAAACGGATAGATgtgcacaaca
4132555 4132570 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 20.5 -50.5 metF
tctggacgtcTAAACGGATAGATGTGcacaacacaa
4132558 4132573 [BCE], [SM]
  MetJ-S-adenosyl-L-methionine repressor metKp Sigma70 -14.5 -143.5 metK
agaattgaccTAAAATAGCCATCCAGatgttaatcc
3086555 3086570 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metKp Sigma70 -2.5 -131.5 metK
aaatagccatCCAGATGTTAATCCATccataccgat
3086567 3086582 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metKp2 Sigma38 -14.5 -143.5 metK
agaattgaccTAAAATAGCCATCCAGatgttaatcc
3086555 3086570 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metKp2 Sigma38 -2.5 -131.5 metK
aaatagccatCCAGATGTTAATCCATccataccgat
3086567 3086582 [AIBSCS] [1]
  MetJ-S-adenosyl-L-methionine repressor metNp Sigma70 -25.5 -94.5 metN, metI, metQ
aacctgattgATTTAGACGTCTGGATgccttaacat
222732 222747 [AIBSCS], [APIORCISFBSCS] [2], [7], [8]
  MetJ-S-adenosyl-L-methionine repressor metNp Sigma70 -17.5 -86.5 metN, metI, metQ
tgatttagacGTCTGGATGCCTTAACatccatttca
222724 222739 [GEA], [AIBSCS] [2], [7]
  MetJ-S-adenosyl-L-methionine repressor metRp1 nd -144.5 -183.5 metR
ttttgaatttAGGGAAGGCGGCAAGTttattcatcc
4012992 4013007 [BPP] [6]
  MetJ-S-adenosyl-L-methionine repressor metRp1 nd -29.5 -68.5 metR
gccgtccagaTGTTTACACATCCATAattggcggtt
4012877 4012892 [BPP] [6]
  MetJ-S-adenosyl-L-methionine repressor metRp2 nd -162.5 -183.5 metR
ttttgaatttAGGGAAGGCGGCAAGTttattcatcc
4012992 4013007 [BPP] [6]
  MetJ-S-adenosyl-L-methionine repressor metRp2 nd -47.5 -68.5 metR
gccgtccagaTGTTTACACATCCATAattggcggtt
4012877 4012892 [BPP] [6]


Alignment and PSSM for MetJ TFBSs    

Aligned TFBS of MetJ   
  Sequence
  GGACGTCAATACATCTGGA
  GGACGTCTAAACGGATAGA
  AGACGTCTGGATGCCTTAA
  GGACATCTAAACTTCTTTG
  AGACATCCAGATAGCTGAA
  AGATGTTAAAACATCGTTA
  AGACGTCCAGATGTAAAGA
  AGATGTTTACACATCCATA
  GGATGGATTAACATCTGGA
  GGACATCTATACTTCCTCC
  AGATGTAAAGATGAAGGAA
  AAACGTATAAGCGTATGTA
  GGATGGCTATTTTAGGTCA
  GGAAGGCGGCAAGTTTATT
  TTTCATCAGCAGATGTTAA

Position weight matrix (PWM). MetJ matrix-quality result   
A	7	1	14	1	4	0	3	4	11	5	13	1	6	2	4	1	4	4	12
C	0	0	0	9	0	0	10	2	0	3	0	8	0	1	8	2	0	2	1
G	7	13	0	0	11	3	0	1	3	4	1	1	6	2	2	3	5	4	1
T	1	1	1	5	0	12	2	8	1	3	1	5	3	10	1	9	6	5	1

Consensus   
;	consensus.strict             	gGACGtCtagAcgtctgga
;	consensus.strict.rc          	TCCAGACGTCTAGACGTCC
;	consensus.IUPAC              	rGAYGtCtarAyrtctkka
;	consensus.IUPAC.rc           	TMMAGAYRTYTAGACRTCY
;	consensus.regexp             	[ag]GA[CT]GtCta[ag]A[ct][ag]tct[gt][gt]a
;	consensus.regexp.rc          	T[AC][AC]AGA[CT][AG]T[CT]TAGAC[AG]TC[CT]

PWM logo   


 


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation




Reference(s)    

 [1] Liu R., Blackwell TW., States DJ., 2001, Conformational model for binding site recognition by the E.coli MetJ transcription factor., Bioinformatics 17(7):622-33

 [2] Marincs F., Manfield IW., Stead JA., McDowall KJ., Stockley PG., 2006, Transcript analysis reveals an extended regulon and the importance of protein-protein co-operativity for the Escherichia coli methionine repressor., Biochem J 396(2):227-34

 [3] Kirby TW., Hindenach BR., Greene RC., 1986, Regulation of in vivo transcription of the Escherichia coli K-12 metJBLF gene cluster., J Bacteriol 165(3):671-7

 [4] Otsuka J., Watanabe H., Mori KT., 1996, Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; suggestion from protein sequence similarities in Escherichia coli., J Theor Biol 178(2):183-204

 [5] Wild CM., McNally T., Phillips SE., Stockley PG., 1996, Effects of systematic variation of the minimal Escherichia coli met consensus operator site: in vivo and in vitro met repressor binding., Mol Microbiol 21(6):1125-35

 [6] Cai XY., Maxon ME., Redfield B., Glass R., Brot N., Weissbach H., 1989, Methionine synthesis in Escherichia coli: effect of the MetR protein on metE and metH expression., Proc Natl Acad Sci U S A 86(12):4407-11

 [7] Gal J., Szvetnik A., Schnell R., Kalman M., 2002, The metD D-methionine transporter locus of Escherichia coli is an ABC transporter gene cluster., J Bacteriol 184(17):4930-2

 [8] Merlin C., Gardiner G., Durand S., Masters M., 2002, The Escherichia coli metD locus encodes an ABC transporter which includes Abc (MetN), YaeE (MetI), and YaeC (MetQ)., J Bacteriol 184(19):5513-7

 [9] Weissbach H., Brot N., 1991, Regulation of methionine synthesis in Escherichia coli., Mol Microbiol 5(7):1593-7

 [10] Somers WS, Phillips SE, 1992, Crystal structure of the met repressor-operator complex at 2.8 A resolution reveals DNA recognition by beta-strands., Nature, 359(6394):387 10.1038/359387a0

 [11] Smith AA., Greene RC., Kirby TW., Hindenach BR., 1985, Isolation and characterization of the product of the methionine-regulatory gene metJ of Escherichia coli K-12., Proc Natl Acad Sci U S A 82(18):6104-8

 [12] Saint-Girons I., Duchange N., Cohen GN., Zakin MM., 1984, Structure and autoregulation of the metJ regulatory gene in Escherichia coli., J Biol Chem 259(22):14282-5

 [13] Phillips SE, Manfield I, Parsons I, Davidson BE, Rafferty JB, Somers WS, Margarita D, Cohen GN, Saint-Girons I, Stockley PG, 1989, Cooperative tandem binding of met repressor of Escherichia coli., Nature, 341(6244):711 10.1038/341711a0

 [14] Belfaiza J, Parsot C, Martel A, de la Tour CB, Margarita D, Cohen GN, Saint-Girons I, 1986, Evolution in biosynthetic pathways: two enzymes catalyzing consecutive steps in methionine biosynthesis originate from a common ancestor and possess a similar regulatory region., Proc Natl Acad Sci U S A, 83(4):867 10.1073/pnas.83.4.867

 [15] Augustus AM, Reardon PN, Spicer LD, 2009, MetJ repressor interactions with DNA probed by in-cell NMR., Proc Natl Acad Sci U S A, 106(13):5065 10.1073/pnas.0811130106

 [16] Hyre DE, Spicer LD, 1995, Thermodynamic evaluation of binding interactions in the methionine repressor system of Escherichia coli using isothermal titration calorimetry., Biochemistry, 34(10):3212 10.1021/bi00010a010

 [17] LaMonte BL, Hughes JA, 2006, In vivo hydrolysis of S-adenosylmethionine induces the met regulon of Escherichia coli., Microbiology (Reading), 152(Pt 5):1451 10.1099/mic.0.28489-0

 [18] Phillips K, Phillips SE, 1994, Electrostatic activation of Escherichia coli methionine repressor., Structure, 2(4):309 10.1016/s0969-2126(00)00032-0

 [19] Parsons ID, Persson B, Mekhalfia A, Blackburn GM, Stockley PG, 1995, Probing the molecular mechanism of action of co-repressor in the E. coli methionine repressor-operator complex using surface plasmon resonance (SPR)., Nucleic Acids Res, 23(2):211 10.1093/nar/23.2.211

 [20] Marti-Arbona R., Teshima M., Anderson PS., Nowak-Lovato KL., Hong-Geller E., Unkefer CJ., Unkefer PJ., 2012, Identification of new ligands for the methionine biosynthesis transcriptional regulator (MetJ) by FAC-MS., J Mol Microbiol Biotechnol 22(4):205-14

 [21] Old IG, Phillips SE, Stockley PG, Saint Girons I, 1991, Regulation of methionine biosynthesis in the Enterobacteriaceae., Prog Biophys Mol Biol, 56(3):145 10.1016/0079-6107(91)90012-h



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