walR

168

two-component response regulator (OmpR family), controls cell wall metabolism

Locus: BSU_40410

Molecular weight: 27.08 kDa

Isoelectric point: 4.88

Protein length: 235 aa

Gene length: 708 bp

Function: control of cell wall metabolism

Product: two-component response regulator (OmpR family)

Essential: yes

Synonyms: walR, yycF

Genomic Context

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List of homologs in different organisms, belongs to COG0745 (Galperin et al., 2021)

Gene

Coordinates: 4,153,696  4,154,403

Phenotypes of a mutant

• essential PubMed
• essentiality can be bypassed by constitutive expression of lytE or cwlO in a pdaC iseA mutant background PubMed
• a constitutively active form of WalR (WalR-R204C) results in constitutive expression of the WalR regulon, and in combination with a ''sepF'' mutation to the formation of cell wall-less L-forms  PubMed

The protein

Protein family

• OmpR family of two-component response regulators

Domains

• Response regulatory domain (aa 4-117) (according to UniProt)

Structure

• 2OQR (PDB) (from Mycobacterium tuberculosis, 48% identity) PubMed
• 2D1V (PDB) (DNA binding domain)2ZWM (PDB) (receiver domain)
• P37478 (AlphaFold)

Modification

• phosphorylated by WalK on Asp-53
• phosphorylated by PrkC on Thr-101, this stimulates WalR activity PubMed

Effectors of protein activity

• phosphorylation likely affects DNA-binding activity

Paralogous protein(s)

• YkoG, YclJ, PhoP

Localization

• cytoplasm (according to Swiss-Prot)

Expression and Regulation

Operons

• Genes: walR-walK-walH-walI-walJ-htrC

  Description: PubMed

  Regulation

  • htrC transcript expressed during sporulation PubMed

Biological materials

Mutant

• MGNA-B828 (yycF::erm), available at the NBRP B. subtilis, Japan

Expression vectors

• pGP2633, constitutive expression in B. subtilis (based on pBQ200), available in Jörg Stülke's lab
• pGP2635, expression of His-WalR in E. coli (based on pWH844), available in Jörg Stülke's lab

Labs working on this gene/protein

• Kevin Devine, Dublin

References

Reviews

Hoch JA A Life in Bacillus subtilis Signal Transduction. Annual review of microbiology. 2017 Sep 08; 71:1-19. doi:10.1146/annurev-micro-030117-020355. PMID:28886686
Devine KM Bacterial L-forms on tap: an improved methodology to generate Bacillus subtilis L-forms heralds a new era of research. Molecular microbiology. 2012 Jan; 83(1):10-3. doi:10.1111/j.1365-2958.2011.07922.x. PMID:22126136
Dubrac S, Bisicchia P, Devine KM, Msadek T A matter of life and death: cell wall homeostasis and the WalKR (YycGF) essential signal transduction pathway. Molecular microbiology. 2008 Dec; 70(6):1307-22. doi:10.1111/j.1365-2958.2008.06483.x. PMID:19019149
Dubrac S, Msadek T Tearing down the wall: peptidoglycan metabolism and the WalK/WalR (YycG/YycF) essential two-component system. Advances in experimental medicine and biology. 2008; 631:214-28. doi:10.1007/978-0-387-78885-2_15. PMID:18792692
Winkler ME, Hoch JA Essentiality, bypass, and targeting of the YycFG (VicRK) two-component regulatory system in gram-positive bacteria. Journal of bacteriology. 2008 Apr; 190(8):2645-8. doi:10.1128/JB.01682-07. PMID:18245295
Fabret C, Feher VA, Hoch JA Two-component signal transduction in Bacillus subtilis: how one organism sees its world. Journal of bacteriology. 1999 Apr; 181(7):1975-83. . PMID:10094672

Original Publications

Matsuoka S, Shimizu Y, Nobe K, Matsumoto K, Asai K, Hara HGlucolipids and lipoteichoic acids affect the activity of SigI, an alternative sigma factor, and WalKR, an essential two-component system, in Bacillus subtilis.Genes to cells : devoted to molecular & cellular mechanisms. 2021 Dec 15; . PMID: 34910349
Libby EA, Reuveni S, Dworkin J Multisite phosphorylation drives phenotypic variation in (p)ppGpp synthetase-dependent antibiotic tolerance. Nature communications. 2019 Nov 13; 10(1):5133. doi:10.1038/s41467-019-13127-z. PMID:31723135
Wu X, Song Q, Han A Interacting proteins of the essential two-component system YycFG in Bacillus subtilis. Journal of basic microbiology. 2019 Jul 24; . doi:10.1002/jobm.201800701. PMID:31339578
Takada H, Shiwa Y, Takino Y, Osaka N, Ueda S, Watanabe S, Chibazakura T, Su'etsugu M, Utsumi R, Yoshikawa H Essentiality of WalRK for growth in Bacillus subtilis and its role during heat stress. Microbiology (Reading, England). 2018 Apr; 164(4):670-684. doi:10.1099/mic.0.000625. PMID:29465029
Libby EA, Goss LA, Dworkin J The Eukaryotic-Like Ser/Thr Kinase PrkC Regulates the Essential WalRK Two-Component System in Bacillus subtilis. PLoS genetics. 2015 Jun; 11(6):e1005275. doi:10.1371/journal.pgen.1005275. PMID:26102633
Dhiman A, Bhatnagar S, Kulshreshtha P, Bhatnagar R Functional characterization of WalRK: A two-component signal transduction system from Bacillus anthracis. FEBS open bio. 2014; 4:65-76. doi:10.1016/j.fob.2013.12.005. PMID:24490131
Huang WZ, Wang JJ, Chen HJ, Chen JT, Shaw GC The heat-inducible essential response regulator WalR positively regulates transcription of sigI, mreBH and lytE in Bacillus subtilis under heat stress. Research in microbiology. 2013 Dec; 164(10):998-1008. doi:10.1016/j.resmic.2013.10.003. pii:S0923-2508(13)00188-5. PMID:24125693
Huang WZ, Wang JJ, Chen HJ, Chen JT, Shaw GC The heat-inducible essential response regulator WalR positively regulates transcription of sigI, mreBH and lytE in Bacillus subtilis under heat stress. Research in microbiology. 2013 Dec; 164(10):998-1008. doi:10.1016/j.resmic.2013.10.003. pii:S0923-2508(13)00188-5. PMID:24125693
Domínguez-Cuevas P, Mercier R, Leaver M, Kawai Y, Errington J The rod to L-form transition of Bacillus subtilis is limited by a requirement for the protoplast to escape from the cell wall sacculus. Molecular microbiology. 2012 Jan; 83(1):52-66. doi:10.1111/j.1365-2958.2011.07920.x. PMID:22122227
Doi A, Okajima T, Gotoh Y, Tanizawa K, Utsumi R X-ray crystal structure of the DNA-binding domain of response regulator WalR essential to the cell viability of staphylococcus aureus and interaction with target DNA. Bioscience, biotechnology, and biochemistry. 2010; 74(9):1901-7. . PMID:20834167
Jende I, Varughese KI, Devine KM Amino acid identity at one position within the alpha1 helix of both the histidine kinase and the response regulator of the WalRK and PhoPR two-component systems plays a crucial role in the specificity of phosphotransfer. Microbiology (Reading, England). 2010 Jun; 156(Pt 6):1848-59. doi:10.1099/mic.0.037515-0. PMID:20167622
Gotoh Y, Doi A, Furuta E, Dubrac S, Ishizaki Y, Okada M, Igarashi M, Misawa N, Yoshikawa H, Okajima T, Msadek T, Utsumi R Novel antibacterial compounds specifically targeting the essential WalR response regulator. The Journal of antibiotics. 2010 Mar; 63(3):127-34. doi:10.1038/ja.2010.4. PMID:20111065
Okajima T, Doi A, Okada A, Gotoh Y, Tanizawa K, Utsumi R Response regulator YycF essential for bacterial growth: X-ray crystal structure of the DNA-binding domain and its PhoB-like DNA recognition motif. FEBS letters. 2008 Oct 15; 582(23-24):3434-8. doi:10.1016/j.febslet.2008.09.007. PMID:18789936
Fukushima T, Szurmant H, Kim EJ, Perego M, Hoch JA A sensor histidine kinase co-ordinates cell wall architecture with cell division in Bacillus subtilis. Molecular microbiology. 2008 Aug; 69(3):621-32. doi:10.1111/j.1365-2958.2008.06308.x. PMID:18573169
King-Scott J, Nowak E, Mylonas E, Panjikar S, Roessle M, Svergun DI, Tucker PA The structure of a full-length response regulator from Mycobacterium tuberculosis in a stabilized three-dimensional domain-swapped, activated state. The Journal of biological chemistry. 2007 Dec 28; 282(52):37717-29. . PMID:17942407
Dubrac S, Boneca IG, Poupel O, Msadek T New insights into the WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. Journal of bacteriology. 2007 Nov; 189(22):8257-69. . PMID:17827301
McLaughlin PD, Bobay BG, Regel EJ, Thompson RJ, Hoch JA, Cavanagh J Predominantly buried residues in the response regulator Spo0F influence specific sensor kinase recognition. FEBS letters. 2007 Apr 03; 581(7):1425-9. . PMID:17350627
Szurmant H, Nelson K, Kim EJ, Perego M, Hoch JA YycH regulates the activity of the essential YycFG two-component system in Bacillus subtilis. Journal of bacteriology. 2005 Aug; 187(15):5419-26. . PMID:16030236
Fabret C, Feher VA, Hoch JA Two-component signal transduction in Bacillus subtilis: how one organism sees its world. Journal of bacteriology. 1999 Apr; 181(7):1975-83. . PMID:10094672
Fabret C, Hoch JA A two-component signal transduction system essential for growth of Bacillus subtilis: implications for anti-infective therapy. Journal of bacteriology. 1998 Dec; 180(23):6375-83. . PMID:9829949

The WalR regulon

Salzberg LI, Powell L, Hokamp K, Botella E, Noone D, Devine KM The WalRK (YycFG) and σ(I) RsgI regulators cooperate to control CwlO and LytE expression in exponentially growing and stressed Bacillus subtilis cells. Molecular microbiology. 2013 Jan; 87(1):180-95. doi:10.1111/mmi.12092. PMID:23199363
Bisicchia P, Noone D, Lioliou E, Howell A, Quigley S, Jensen T, Jarmer H, Devine KM The essential YycFG two-component system controls cell wall metabolism in Bacillus subtilis. Molecular microbiology. 2007 Jul; 65(1):180-200. . PMID:17581128
Howell A, Dubrac S, Andersen KK, Noone D, Fert J, Msadek T, Devine K Genes controlled by the essential YycG/YycF two-component system of Bacillus subtilis revealed through a novel hybrid regulator approach. Molecular microbiology. 2003 Sep; 49(6):1639-55. . PMID:12950927
Fukuchi K, Kasahara Y, Asai K, Kobayashi K, Moriya S, Ogasawara N The essential two-component regulatory system encoded by yycF and yycG modulates expression of the ftsAZ operon in Bacillus subtilis. Microbiology (Reading, England). 2000 Jul; 146 ( Pt 7):1573-83. . PMID:10878122