PotN represents a novel energy-state sensing PII subfamily, occurring in firmicutes.

Lentilactobacillus hilgardii PII-like protein PotN pyruvate/2-oxoglutarate/acetoin dehydrogenase AcoB transcription factor GlnR transporter of polyamines PotABCD

Journal

The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646

Informations de publication

Date de publication:
09 2022
Historique:
revised: 19 02 2022
received: 09 04 2021
accepted: 10 03 2022
pubmed: 15 3 2022
medline: 9 9 2022
entrez: 14 3 2022
Statut: ppublish

Résumé

PII proteins are signal processor proteins that regulate the cellular metabolism of Bacteria, Archea and plant chloroplasts typically in response to the cellular nitrogen status. Here, we report the first biochemical characterization of a novel PII-like protein PotN from Lentilactobacillus hilgardii. PotN is encoded in an operon together with the potABCD genes, encoding the ABC transporter for spermidine/putrescine. Like canonical PII proteins, the native PotN has a trimeric structure and competitively binds ATP and ADP, but it does not bind 2-oxoglutarate. Immunoprecipitation and pull-down experiments revealed that PotN is associated in vivo with the transcriptional regulator GlnR and the beta-subunit of pyruvate/2-oxoglutarate/acetoin dehydrogenase AcoB. Moreover, in vitro assays revealed that the ATPase domain of PotA also is able to interact with PotN. Interaction analyses demonstrated that PotN preferentially associates with PotA in the ADP state, whereas it binds to GlnR at elevated ATP levels. This suggests that PotN regulates the transport of polyamines and GlnR-dependent gene expression in response to the energy availability for the cell.

Identifiants

pubmed: 35285159
doi: 10.1111/febs.16431
doi:

Substances chimiques

Bacterial Proteins 0
Ketoglutaric Acids 0
PII Nitrogen Regulatory Proteins 0
Adenosine Diphosphate 61D2G4IYVH
Adenosine Triphosphate 8L70Q75FXE
Nitrogen N762921K75

Banques de données

RefSeq
['QIR10170', 'AIS03498', 'SBW30903', 'CAB15669', 'SQE56252', 'AAC73553', 'AAC75606', 'AAF42322', 'AFK17834', 'AFK17836', 'WP_042707534', 'AEA46717', 'BAD79382', 'AEE8209']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5305-5321

Informations de copyright

© 2022 Federation of European Biochemical Societies.

Références

Forchhammer K. P-II signal transducers: novel functional and structural insights. Trends Microbiol. 2008;16:65-72.
Forchhammer K, Lüddecke J. Sensory properties of the PII signalling protein family. FEBS J. 2016;283:425-37.
Truan D, Bjelic S, Li XD, Winkler FK. Structure and thermodynamics of effector molecule binding to the nitrogen signal transduction P-II protein GInZ from Azospirillum brasilense. J Mol Biol. 2014;426:2783-99.
Zeth K, Fokina O, Forchhammer K. Structural basis and target-specific modulation of ADP sensing by the Synechococcus elongatus PII signaling protein. J Biol Chem. 2014;289:8960-72.
Fokina O, Chellamuthu VR, Zeth K, Forchhammer K. A novel signal transduction protein P-II variant from Synechococcus elongatus PCC 7942 indicates a two-step process for NAGK-P-II complex formation. J Mol Biol. 2010;399:410-21.
Truan D, Huergo LF, Chubatsu LS, Merrick M, Li XD, Winkler FK. A new P-II protein structure identifies the 2-oxoglutarate binding site. J Mol Biol. 2010;400:531-9.
Fokina O, Chellamuthu VR, Forchhammer K, Zeth K. Mechanism of 2-oxoglutarate signaling by the Synechococcus elongatus P-II signal transduction protein. Proc Natl Acad Sci USA. 2010;107:19760-5.
Reitzer L. Nitrogen assimilation and global regulation in Escherichia coli. Annu Rev Microbiol. 2003;57:155-76.
Ninfa AJ, Jiang P. PII signal transduction proteins: sensors of alpha-ketoglutarate that regulate nitrogen metabolism. Curr Opin Microbiol. 2005;8:168-73.
Merrick M. Post-translational modification of P-II signal transduction proteins. Front Microbiol. 2015;5:763.
Atkinson MR, Blauwkamp TA, Ninfa AJ. Context-dependent functions of the PII and GlnK signal transduction proteins in Escherichia coli. J Bacteriol. 2002;184:5364-75.
Ninfa AJ, Jiang P. Sensation of alpha-ketoglutarate, adenylate energy charge and glutamine and signal integration by the nitrogen assimilation control system of Escherichia coli. In: Spiro S, Dixon R, editors. Sensory mechanisms in bacteria: molecular aspects of signal recognition. Poole, UK: Caister Academic Press, Lytchett Matravers; 2010:61-80.
Bourrellier ABF, Valot B, Guillot A, Ambard-Bretteville F, Vidal J, Hodges M. Chloroplast acetyl-CoA carboxylase activity is 2-oxoglutarate-regulated by interaction of PII with the biotin carboxyl carrier subunit. Proc Natl Acad Sci USA. 2010;107:502-7.
Gerhardt ECM, Rodrigues TE, Muller-Santos M, Pedrosa FO, Souza EM, Forchhammer K, et al. The Bacterial signal transduction protein GlnB regulates the committed step in fatty acid biosynthesis by acting as a dissociable regulatory subunit of acetyl-CoA carboxylase. Mol Microbiol. 2015;95:1025-35.
Rodionova IA, Goodacre N, Babu M, Emili A, Uetz P, Saier MH. The nitrogen regulatory PII protein (GlnB) and N-acetylglucosamine 6-phosphate epimerase (NanE) allosterically activate glucosamine 6-phosphate deaminase (NagB) in Escherichia coli. J Bacteriol. 2018;200:e00691-17.
Schubert C, Zedler S, Strecker A, Unden G. L-aspartate as a high-quality nitrogen source in Escherichia coli: regulation of L-aspartase by the nitrogen regulatory system and interaction of L-aspartase with GlnB. Mol Microbiol. 2021;115:526-38.
Conroy MJ, Durand A, Lupo D, Li XD, Bullough PA, Winkler FK, et al. The crystal structure of the Escherichia coli AmtB-GlnK complex reveals how GlnK regulates the ammonia channel. Proc Natl Acad Sci USA. 2007;104:1213-8.
Tremblay PL, Hallenbeck PC. Ammonia-induced formation of an AmtB-GlnK complex is not sufficient for nitrogenase regulation in the photosynthetic bacterium Rhodobacter capsulatus. J Bacteriol. 2008;190:1588-94.
Radchenko MV, Thornton J, Merrick M. Control of AmtB-GlnK complex formation by intracellular levels of ATP, ADP, and 2-oxoglutarate. J Biol Chem. 2010;285:31037-45.
Radchenko MV, Thornton J, Merrick M. Association and dissociation of the GlnK-AmtB complex in response to cellular nitrogen status can occur in the absence of GlnK post-translational modification. Front Microbiol. 2014;5:731.
Javelle A, Severi E, Thornton J, Merrick M. Ammonium sensing in Escherichia coli - role of the ammonium transporter AmtB and AmtB-GlnK complex formation. J Biol Chem. 2004;279:8530-8.
Maheswaran M, Urbanke C, Forchhammer K. Complex formation and catalytic activation by the P-II signaling protein of N-acetyl-L-glutamate kinase from Synechococcus elongatus strain PCC 7942. J Biol Chem. 2004;279:55202-10.
Maheswaran M, Ziegler K, Lockau W, Hagemann M, Forchhammer K. P-II-regulated arginine synthesis controls accumulation of cyanophycin in Synechocystis sp strain PCC 6803. J Bacteriol. 2006;188:2730-4.
Espinosa J, Forchhammer K, Burillo S, Contreras A. Interaction network in cyanobacterial nitrogen regulation: PipX, a protein that interacts in a 2-oxoglutarate dependent manner with PII and NtcA. Mol Microbiol. 2006;61:457-69.
Llacer JL, Espinosa J, Castells MA, Contreras A, Forchhammer K, Rubio V. Structural basis for the regulation of NtcA-dependent transcription by proteins PipX and PII. Proc Natl Acad Sci USA. 2010;107:15397-402.
Orthwein T, Scholl J, Spat P, Lucius S, Koch M, Macek B, et al. The novel P-II-interactor PirC identifies phosphoglycerate mutase as key control point of carbon storage metabolism in cyanobacteria. Proc Natl Acad Sci USA. 2021;118:e2019988118.
Scholl J, Dengler L, Bader L, Forchhammer K. Phosphoenolpyruvate carboxylase from the cyanobacterium Synechocystis sp. PCC 6803 is under global metabolic control by P-II signaling. Mol Microbiol. 2020;114:292-307.
Chellamuthu VR, Ermilova E, Lapina T, Lüddecke J, Minaeva E, Herrmann C, et al. A widespread glutamine-sensing mechanism in the plant kingdom. Cell. 2014;159:1188-99.
Forchhammer K, Selim K, Huergo L. New views on PII signaling: from nitrogen sensing to global metabolic control. Trends Microbiol. 2022;in press. https://doi.org/10.1016/j.tim.2021.12.014
Amon J, Titgemeyer F, Burkovski A. Common patterns - unique features: nitrogen metabolism and regulation in Gram-positive bacteria. FEMS Microbiol Rev. 2010;34:588-605.
Fisher SH, Brandenburg JL, Wray LV. Mutations in Bacillus subtilis glutamine synthetase that block its interaction with transcription factor TnrA. Mol Microbiol. 2002;45:627-35.
Fisher SH, Wray LV. Bacillus subtilis glutamine synthetase regulates its own synthesis by acting as a chaperone to stabilize GInR-DNA complexes. Proc Natl Acad Sci USA. 2008;105:1014-9.
Wray LV, Fisher SH. Bacillus subtilis GlnR contains an autoinhibitory C-terminal domain required for the interaction with glutamine synthetase. Mol Microbiol. 2008;68:277-85.
Wray LV, Zalieckas JM, Fisher SH. Bacillus subtilis glutamine synthetase controls gene expression through a protein-protein interaction with transcription factor TnrA. Cell. 2001;107:427-35.
Fisher SH. Regulation of nitrogen metabolism in Bacillus subtilis: vive la difference! Mol Microbiol. 1999;32:223-32.
Wray LV, Ferson AE, Rohrer K, Fisher SH. TnrA, a transcription factor required for global nitrogen regulation in Bacillus subtilis. Proc Natl Acad Sci USA. 1996;93:8841-5.
Detsch C, Stulke J. Ammonium utilization in Bacillus subtilis: transport and regulatory functions of NrgA and NrgB. Microbiology (Reading). 2003;149:3289-97.
Heinrich A, Woyda K, Brauburger K, Meiss G, Detsch C, Stulke J, et al. Interaction of the membrane-bound GlnK-AmtB complex with the master regulator of nitrogen metabolism TnrA in Bacillus subtilis. J Biol Chem. 2006;281:34909-17.
Kayumov A, Heinrich A, Sharipova M, Iljinskaya O, Forchhammer K. Inactivation of the general transcription factor TnrA in Bacillus subtilis by proteolysis. Microbiology (Reading). 2008;154:2348-55.
Kayumov A, Heinrich A, Fedorova K, Ilinskaya O, Forchhammer K. Interaction of the general transcription factor TnrA with the PII-like protein GlnK and glutamine synthetase in Bacillus subtilis. FEBS J. 2011;278:1779-89.
Hauf K, Kayumov A, Gloge F, Forchhammer K. The molecular basis of TnrA control by glutamine synthetase in Bacillus subtilis. J Biol Chem. 2016;291:3483-95.
Gunka K, Commichau FM. Control of glutamate homeostasis in Bacillus subtilis: a complex interplay between ammonium assimilation, glutamate biosynthesis and degradation. Mol Microbiol. 2012;85:213-24.
Chen PM, Chen YYM, Yu SL, Sher S, Lai CH, Chia JS. Role of GlnR in acid-mediated repression of genes encoding proteins involved in glutamine and glutamate metabolism in Streptococcus mutans. Appl Environ Microbiol. 2010;76:2478-86.
Kloosterman TG, Hendriksen WT, Bijlsma JJE, Bootsma HJ, van Hijum S, Kok J, et al. Regulation of glutamine and glutamate metabolism by GlnR and GlnA in Streptococcus pneumoniae. J Biol Chem. 2006;281:25097-109.
Hendriksen WT, Kloosterman TG, Bootsma HJ, Estevao S, de Groot R, Kuipers OP, et al. Site-specific contributions of glutamine-dependent regulator GlnR and GlnR-regulated genes to virulence of Streptococcus pneumoniae. Infect Immun. 2008;76:1230-8.
Wang Y, Wang JZ, Shao ZH, Yuan H, Lu YH, Jiang WH, et al. Three of four GlnR binding sites are essential for GlnR-mediated activation of transcription of the Amycolatopsis mediterranei nas Operon. J Bacteriol. 2013;195:2595-602.
Sant'Anna FH, Ambrosini A, de Souza R, Fernandes GD, Bach E, Balsanelli E, et al. Reclassification of Paenibacillus riograndensis as a Genomovar of Paenibacillus sonchi: genome-based metrics improve bacterial taxonomic classification. Front Microbiol. 2017;8:1849.
Castellen P, Rego FG, Portugal ME, Benelli EM. The Streptococcus mutans GlnR protein exhibits an increased affinity for the glnRA operon promoter when bound to GlnK. Braz J Med Biol Res. 2011;44:1202-8.
Zhuravleva DE, Iskhakova ZI, Ozhegov GD, Gogoleva NE, Khusnutdinova DR, Shagimardanova EI, et al. Complete genome sequence of Lactobacillus hilgardii LMG 7934, carrying the gene encoding for the novel PII-like protein PotN. Curr Microbiol. 2020;77:3538-45.
Forchhammer K, Luddecke J. Sensory properties of the P-II signalling protein family. FEBS J. 2016;283:425-37.
Jiang P, Zucker P, Atkinson MR, Kamberov ES, Tirasophon W, Chandran P, et al. Structure/function analysis of the PII signal transduction protein of Escherichia coli: genetic separation of interactions with protein receptors. J Bacteriol. 1997;179:4342-53.
Zhang CC, Zhou CZ. ATPase as a switch in P-II signal transduction. Proc Natl Acad Sci USA. 2013;110:12863-4.
Bennett BD, Kimball EH, Gao M, Osterhout R, Van Dien SJ, Rabinowitz JD. Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli. Nat Chem Biol. 2009;5:593-9.
Jiang P, Zucker P, Ninfa AJ. Probing interactions of the homotrimeric PII signal transduction protein with its receptors by use of PII heterotrimers formed in vitro from wild-type and mutant subunits. J Bacteriol. 1997;179:4354-60.
Battesti A, Bouveret E. The bacterial two-hybrid system based on adenylate cyclase reconstitution in Escherichia coli. Methods. 2012;58:325-34.
Llacer JL, Contreras A, Forchhammer K, Marco-Marin C, Gil-Ortiz F, Maldonado R, et al. The crystal structure of the complex of P-II and acetylglutamate kinase reveals how P-II controls the storage of nitrogen as arginine. Proc Natl Acad Sci USA. 2007;104:17644-9.
Brown NL, Stoyanov JV, Kidd SP, Hobman JL. The MerR family of transcriptional regulators. FEMS Microbiol Rev. 2003;27:145-63.
Kashiwagi K, Innami A, Zenda R, Tomitori H, Igarashi K. The ATPase activity and the functional domain of PotA, a component of the spermidine-preferential uptake system in Escherichia coli. J Biol Chem. 2002;277:24212-9.
Selim KA, Tremiño L, Marco-Marín C, Alva V, Espinosa J, Contreras A, et al. Functional and structural characterization of PII-like protein CutA does not support involvement in heavy metal tolerance and hints at a small-molecule carrying/signaling role. FEBS J. 2021;288:1142-62.
Huergo LF, Dixon R. The emergence of 2-oxoglutarate as a master regulator metabolite. Microbiol Mol Biol Rev. 2015;79:419-35.
Fernandes GD, Hauf K, Sant'Anna FH, Forchhammer K, Passaglia LMP. Glutamine synthetase stabilizes the binding of GlnR to nitrogen fixation gene operators. FEBS J. 2017;284:903-18.
Lee HM, Flores E, Forchhammer K, Herrero A, de Marsac NT. Phosphorylation of the signal transducer P-II protein and an additional effector are required for the P-II-mediated regulation of nitrate and nitrite uptake in the cyanobacterium Synechococcus sp PCC 7942. Eur J Biochem. 2000;267:591-600.
Kobayashi M, Rodriguez R, Lara C, Omata T. Involvement of the C-terminal domain of an ATP-binding subunit in the regulation of the ABC-type nitrate/nitrite transporter of the cyanobacterium Synechococcus sp. strain PCC 7942. J Biol Chem. 1997;272:27197-201.
Watzer B, Spat P, Neumann N, Koch M, Sobotka R, Macek B, et al. The signal transduction protein P-II controls ammonium, nitrate and urea uptake in cyanobacteria. Front Microbiol. 2019;10:1428.
Krysenko S, Okoniewski N, Kulik A, Matthews A, Grimpo J, Wohlleben W, et al. Gamma-glutamylpolyamine synthetase GlnA3 is involved in the first step of polyamine degradation pathway in Streptomyces coelicolor M145. Front Microbiol. 2017;8:726.
Kayumov AR, Fedorova KP, Il'inskaya ON, Sharipova MR. Content and localization of TNRA and GLNK regulatory proteins in the cells of Bacillus subtilis under nitrogen starvation. Mol Biol. 2010;44:655-7.
Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, Smith HO. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods. 2009;6:343-U41.
Fedorova K, Kayumov A, Woyda K, Ilinskaja O, Forchhammer K. Transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in Bacillus subtilis. FEBS Lett. 2013;587:1293-1298.
Orkin S. Molecular-cloning - a laboratory manual, 2nd edition - Sambrook,J, Fritsch,EF, Maniatis,T. Nature. 1990;343:604-605.
Miller JH. Experiments in molecular genetics: assay of β-galactosidase. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1972. p. 352-355.
Madeira F, Park YM, Lee J, Buso N, Gur T, Madhusoodanan N, et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res. 2019;47:W636-W641.
Felsenstein J. Confidence limits on phylogenies: an approach using the bootstrap. Evolution. 1985;39:783-791.
Nei M, Kumar S. Molecular evolution and phylogenetics. Oxford: Oxford University Press; 2000.
Tamura K, Stecher G, Kumar S. MEGA11: molecular evolutionary genetics analysis version 11. Mol Biol Evol. 2021;38:3022-3027.

Auteurs

Zalina I Iskhakova (ZI)

Department of Genetics, Kazan Federal University, Russia.

Darya E Zhuravleva (DE)

Department of Genetics, Kazan Federal University, Russia.

Christopher Heim (C)

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.

Marcus D Hartmann (MD)

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Tübingen, Germany.

Aleksandr V Laykov (AV)

Department of Genetics, Kazan Federal University, Russia.

Karl Forchhammer (K)

Institut für Mikrobiologie, Eberhard-Karls-Universität Tübingen, Germany.

Airat R Kayumov (AR)

Department of Genetics, Kazan Federal University, Russia.

Articles similaires

Photosynthesis Ribulose-Bisphosphate Carboxylase Carbon Dioxide Molecular Dynamics Simulation Cyanobacteria
Adenosine Triphosphate Adenosine Diphosphate Mitochondrial ADP, ATP Translocases Binding Sites Mitochondria

Two codependent routes lead to high-level MRSA.

Abimbola Feyisara Adedeji-Olulana, Katarzyna Wacnik, Lucia Lafage et al.
1.00
Methicillin-Resistant Staphylococcus aureus Penicillin-Binding Proteins Peptidoglycan Bacterial Proteins Anti-Bacterial Agents
Soil Charcoal Nutrients Manure Nitrogen

Classifications MeSH