Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 293 (5530): 705-708

Copyright © 2001 by the American Association for the Advancement of Science

Role of Inorganic Polyphosphate in Promoting Ribosomal Protein Degradation by the Lon Protease in E. coli

Akio Kuroda,1* Kazutaka Nomura,1 Ryo Ohtomo,2 Junichi Kato,1 Tsukasa Ikeda,1 Noboru Takiguchi,1 Hisao Ohtake,1 Arthur Kornberg2

Inorganic polyphosphate (polyP), a polymer of hundreds of phosphate (Pi) residues, accumulates in Escherichia coli in response to stresses, including amino acid starvation. Here we show that the adenosine 5'-triphosphate-dependent protease Lon formed a complex with polyP and degraded most of the ribosomal proteins, including S2, L9, and L13. Purified S2 also bound to polyP and formed a complex with Lon in the presence of polyP. Thus, polyP may promote ribosomal protein degradation by the Lon protease, thereby supplying the amino acids needed to respond to starvation.

1 Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-4-1 Kagamiyama, Hiroshima 739-8527, Japan.
2 Department of Biochemistry, Stanford University, Stanford, CA 94305-5307, USA.
*   To whom correspondence should be addressed. E-mail: akuroda{at}

Metabolomic and transcriptomic stress response of Escherichia coli.
S. Jozefczuk, S. Klie, G. Catchpole, J. Szymanski, A. Cuadros-Inostroza, D. Steinhauser, J. Selbig, and L. Willmitzer (2014)
Mol Syst Biol 6, 364
   Abstract »    Full Text »    PDF »
A New Subfamily of Polyphosphate Kinase 2 (Class III PPK2) Catalyzes both Nucleoside Monophosphate Phosphorylation and Nucleoside Diphosphate Phosphorylation.
K. Motomura, R. Hirota, M. Okada, T. Ikeda, T. Ishida, and A. Kuroda (2014)
Appl. Envir. Microbiol. 80, 2602-2608
   Abstract »    Full Text »    PDF »
The inoculum effect and band-pass bacterial response to periodic antibiotic treatment.
C. Tan, R. Phillip Smith, J. K. Srimani, K. A. Riccione, S. Prasada, M. Kuehn, and L. You (2014)
Mol Syst Biol 8, 617
   Abstract »    Full Text »    PDF »
Accumulation of Polyphosphate in Lactobacillus spp. and Its Involvement in Stress Resistance.
C. Alcantara, A. Blasco, M. Zuniga, and V. Monedero (2014)
Appl. Envir. Microbiol. 80, 1650-1659
   Abstract »    Full Text »    PDF »
Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters.
S. Helaine, A. M. Cheverton, K. G. Watson, L. M. Faure, S. A. Matthews, and D. W. Holden (2014)
Science 343, 204-208
   Abstract »    Full Text »    PDF »
Chromosome replication and segregation govern the biogenesis and inheritance of inorganic polyphosphate granules.
J. T. Henry and S. Crosson (2013)
Mol. Biol. Cell 24, 3177-3186
   Abstract »    Full Text »    PDF »
Molecular mechanisms of multiple toxin-antitoxin systems are coordinated to govern the persister phenotype.
R. A. Fasani and M. A. Savageau (2013)
PNAS 110, E2528-E2537
   Abstract »    Full Text »    PDF »
Diurnal Changes of Polysome Loading Track Sucrose Content in the Rosette of Wild-Type Arabidopsis and the Starchless pgm Mutant.
S. K. Pal, M. Liput, M. Piques, H. Ishihara, T. Obata, M. C. M. Martins, R. Sulpice, J. T. van Dongen, A. R. Fernie, U. P. Yadav, et al. (2013)
Plant Physiology 162, 1246-1265
   Abstract »    Full Text »    PDF »
Polyphosphate Deficiency in Mycobacterium tuberculosis Is Associated with Enhanced Drug Susceptibility and Impaired Growth in Guinea Pigs.
R. Singh, M. Singh, G. Arora, S. Kumar, P. Tiwari, and S. Kidwai (2013)
J. Bacteriol. 195, 2839-2851
   Abstract »    Full Text »    PDF »
FtsH-Mediated Coordination of Lipopolysaccharide Biosynthesis in Escherichia coli Correlates with the Growth Rate and the Alarmone (p)ppGpp.
M. Schakermann, S. Langklotz, and F. Narberhaus (2013)
J. Bacteriol. 195, 1912-1919
   Abstract »    Full Text »    PDF »
Isolation of Highly Persistent Mutants of Salmonella enterica Serovar Typhimurium Reveals a New Toxin-Antitoxin Module.
A. Slattery, A. H. Victorsen, A. Brown, K. Hillman, and G. J. Phillips (2013)
J. Bacteriol. 195, 647-657
   Abstract »    Full Text »    PDF »
Environmental perturbations lift the degeneracy of the genetic code to regulate protein levels in bacteria.
A. R. Subramaniam, T. Pan, and P. Cluzel (2013)
PNAS 110, 2419-2424
   Abstract »    Full Text »    PDF »
A Single Missense Mutation in a Coiled-Coil Domain of Escherichia coli Ribosomal Protein S2 Confers a Thermosensitive Phenotype That Can Be Suppressed by Ribosomal Protein S1.
L. V. Aseev, A. O. Chugunov, R. G. Efremov, and I. V. Boni (2013)
J. Bacteriol. 195, 95-104
   Abstract »    Full Text »    PDF »
Conditional cooperativity in toxin-antitoxin regulation prevents random toxin activation and promotes fast translational recovery.
I. Cataudella, A. Trusina, K. Sneppen, K. Gerdes, and N. Mitarai (2012)
Nucleic Acids Res. 40, 6424-6434
   Abstract »    Full Text »    PDF »
Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription.
M. D. Jimenez-Nunez, D. Moreno-Sanchez, L. Hernandez-Ruiz, A. Benitez-Rondan, A. Ramos-Amaya, B. Rodriguez-Bayona, F. Medina, J. A. Brieva, and F. A. Ruiz (2012)
Haematologica 97, 1264-1271
   Abstract »    Full Text »    PDF »
Opposing effects of DNA on proteolysis of a replication initiator.
S. Kubik, K. Wegrzyn, M. Pierechod, and I. Konieczny (2012)
Nucleic Acids Res. 40, 1148-1159
   Abstract »    Full Text »    PDF »
ppGpp and Polyphosphate Modulate Cell Cycle Progression in Caulobacter crescentus.
C. C. Boutte, J. T. Henry, and S. Crosson (2012)
J. Bacteriol. 194, 28-35
   Abstract »    Full Text »    PDF »
A Specific Inorganic Triphosphatase from Nitrosomonas europaea: STRUCTURE AND CATALYTIC MECHANISM.
D. Delvaux, M. R. V. S. Murty, V. Gabelica, B. Lakaye, V. V. Lunin, T. Skarina, O. Onopriyenko, G. Kohn, P. Wins, E. De Pauw, et al. (2011)
J. Biol. Chem. 286, 34023-34035
   Abstract »    Full Text »    PDF »
Regulatory role of cardiolipin in the activity of an ATP-dependent protease, Lon, from Escherichia coli.
N. Minami, T. Yasuda, Y. Ishii, K. Fujimori, and F. Amano (2011)
J. Biochem. 149, 519-527
   Abstract »    Full Text »    PDF »
Polyphosphate Accumulation in Escherichia coli in Response to Defects in DNA Metabolism.
L. Amado and A. Kuzminov (2009)
J. Bacteriol. 191, 7410-7416
   Abstract »    Full Text »    PDF »
Tracking insertion mutants within libraries by deep sequencing and a genome-wide screen for Haemophilus genes required in the lung.
J. D. Gawronski, S. M. S. Wong, G. Giannoukos, D. V. Ward, and B. J. Akerley (2009)
PNAS 106, 16422-16427
   Abstract »    Full Text »    PDF »
Removal of a ribosome small subunit-dependent GTPase confers salt resistance on Escherichia coli cells.
Y. Hase, S. Yokoyama, A. Muto, and H. Himeno (2009)
RNA 15, 1766-1774
   Abstract »    Full Text »    PDF »
ATP-dependent Proteases Differ Substantially in Their Ability to Unfold Globular Proteins.
P. Koodathingal, N. E. Jaffe, D. A. Kraut, S. Prakash, S. Fishbain, C. Herman, and A. Matouschek (2009)
J. Biol. Chem. 284, 18674-18684
   Abstract »    Full Text »    PDF »
Phosphate-Enhanced Stationary-Phase Fitness of Escherichia coli Is Related to Inorganic Polyphosphate Level.
L. A. Schurig-Briccio, R. N. Farias, M. R. Rintoul, and V. A. Rapisarda (2009)
J. Bacteriol. 191, 4478-4481
   Abstract »    Full Text »    PDF »
Exopolyphosphatases PPX1 and PPX2 from Corynebacterium glutamicum.
S. N. Lindner, S. Knebel, H. Wesseling, S. M. Schoberth, and V. F. Wendisch (2009)
Appl. Envir. Microbiol. 75, 3161-3170
   Abstract »    Full Text »    PDF »
Regulation of ribonuclease E activity by the L4 ribosomal protein of Escherichia coli.
D. Singh, S.-J. Chang, P.-H. Lin, O. V. Averina, V. R. Kaberdin, and S. Lin-Chao (2009)
PNAS 106, 864-869
   Abstract »    Full Text »    PDF »
Role of Polyphosphates in Microbial Adaptation to Extreme Environments.
M. J. Seufferheld, H. M. Alvarez, and M. E. Farias (2008)
Appl. Envir. Microbiol. 74, 5867-5874
   Full Text »    PDF »
A new regulatory circuit in ribosomal protein operons: S2-mediated control of the rpsB-tsf expression in vivo.
L. V. Aseev, A. A. Levandovskaya, L. S. Tchufistova, N. V. Scaptsova, and I. V. Boni (2008)
RNA 14, 1882-1894
   Abstract »    Full Text »    PDF »
Bacterial Growth and Cell Division: a Mycobacterial Perspective.
E. C. Hett and E. J. Rubin (2008)
Microbiol. Mol. Biol. Rev. 72, 126-156
   Abstract »    Full Text »    PDF »
Cordycepin-hypersensitive growth links elevated polyphosphate levels to inhibition of poly(A) polymerase in Saccharomyces cerevisiae.
S. Holbein, F. M. Freimoser, T. P. Werner, A. Wengi, and B. Dichtl (2008)
Nucleic Acids Res. 36, 353-363
   Abstract »    Full Text »    PDF »
Transcription Profiling of the Stringent Response in Escherichia coli.
T. Durfee, A.-M. Hansen, H. Zhi, F. R. Blattner, and D. J. Jin (2008)
J. Bacteriol. 190, 1084-1096
   Abstract »    Full Text »    PDF »
The Bacterial Stringent Response, Conserved in Chloroplasts, Controls Plant Fertilization.
S. Masuda, K. Mizusawa, T. Narisawa, Y. Tozawa, H. Ohta, and K.-i. Takamiya (2008)
Plant Cell Physiol. 49, 135-141
   Abstract »    Full Text »    PDF »
Polyphosphate Kinase 1 Is a Pathogenesis Determinant in Campylobacter jejuni.
H. L. Candon, B. J. Allan, C. D. Fraley, and E. C. Gaynor (2007)
J. Bacteriol. 189, 8099-8108
   Abstract »    Full Text »    PDF »
Polyphosphate kinase 1, a conserved bacterial enzyme, in a eukaryote, Dictyostelium discoideum, with a role in cytokinesis.
H. Zhang, M. R. Gomez-Garcia, X. Shi, N. N. Rao, and A. Kornberg (2007)
PNAS 104, 16486-16491
   Abstract »    Full Text »    PDF »
Lon Protease Degrades Transfer-Messenger RNA-Tagged Proteins.
J. S. Choy, L. L. Aung, and A. W. Karzai (2007)
J. Bacteriol. 189, 6564-6571
   Abstract »    Full Text »    PDF »
NCgl2620 Encodes a Class II Polyphosphate Kinase in Corynebacterium glutamicum.
S. N. Lindner, D. Vidaurre, S. Willbold, S. M. Schoberth, and V. F. Wendisch (2007)
Appl. Envir. Microbiol. 73, 5026-5033
   Abstract »    Full Text »    PDF »
Targeted Protein Degradation by Salmonella under Phagosome-mimicking Culture Conditions Investigated Using Comparative Peptidomics.
N. P. Manes, J. K. Gustin, J. Rue, H. M. Mottaz, S. O. Purvine, A. D. Norbeck, M. E. Monroe, J. S. D. Zimmer, T. O. Metz, J. N. Adkins, et al. (2007)
Mol. Cell. Proteomics 6, 717-727
   Abstract »    Full Text »    PDF »
Kinetic and Mutational Analyses of the Major Cytosolic Exopolyphosphatase from Saccharomyces cerevisiae.
M. Tammenkoski, V. M. Moiseev, M. Lahti, E. Ugochukwu, T. H. C. Brondijk, S. A. White, R. Lahti, and A. A. Baykov (2007)
J. Biol. Chem. 282, 9302-9311
   Abstract »    Full Text »    PDF »
The Lon protease of Pseudomonas aeruginosa is induced by aminoglycosides and is involved in biofilm formation and motility.
A. K. Marr, J. Overhage, M. Bains, and R. E. W. Hancock (2007)
Microbiology 153, 474-482
   Abstract »    Full Text »    PDF »
Conservation of the metabolomic response to starvation across two divergent microbes.
M. J. Brauer, J. Yuan, B. D. Bennett, W. Lu, E. Kimball, D. Botstein, and J. D. Rabinowitz (2006)
PNAS 103, 19302-19307
   Abstract »    Full Text »    PDF »
Diverse Phenotypes Resulting from Polyphosphate Kinase Gene (ppk1) Inactivation in Different Strains of Helicobacter pylori.
S. Tan, C. D. Fraley, M. Zhang, D. Dailidiene, A. Kornberg, and D. E. Berg (2005)
J. Bacteriol. 187, 7687-7695
   Abstract »    Full Text »    PDF »
Direct Labeling of Polyphosphate at the Ultrastructural Level in Saccharomyces cerevisiae by Using the Affinity of the Polyphosphate Binding Domain of Escherichia coli Exopolyphosphatase.
K. Saito, R. Ohtomo, Y. Kuga-Uetake, T. Aono, and M. Saito (2005)
Appl. Envir. Microbiol. 71, 5692-5701
   Abstract »    Full Text »    PDF »
Inorganic polyphosphate in the social life of Myxococcus xanthus: Motility, development, and predation.
H. Zhang, N. N. Rao, T. Shiba, and A. Kornberg (2005)
PNAS 102, 13416-13420
   Abstract »    Full Text »    PDF »
Autophagy Is Required for Maintenance of Amino Acid Levels and Protein Synthesis under Nitrogen Starvation.
J. Onodera and Y. Ohsumi (2005)
J. Biol. Chem. 280, 31582-31586
   Abstract »    Full Text »    PDF »
Borrelia burgdorferi rel Is Responsible for Generation of Guanosine-3'-Diphosphate-5'-Triphosphate and Growth Control.
J. V. Bugrysheva, A. V. Bryksin, H. P. Godfrey, and F. C. Cabello (2005)
Infect. Immun. 73, 4972-4981
   Abstract »    Full Text »    PDF »
Crystal structure of a polyphosphate kinase and its implications for polyphosphate synthesis.
Y. Zhu, W. Huang, S. S. K. Lee, and W. Xu (2005)
EMBO Rep. 6, 681-687
   Abstract »    Full Text »    PDF »
Polyphosphate Kinase Protects Salmonella enterica from Weak Organic Acid Stress.
M. Price-Carter, T. G. Fazzio, E. I. Vallbona, and J. R. Roth (2005)
J. Bacteriol. 187, 3088-3099
   Abstract »    Full Text »    PDF »
Inorganic polyphosphate in the origin and survival of species.
M. R. W. Brown and A. Kornberg (2004)
PNAS 101, 16085-16087
   Abstract »    Full Text »    PDF »
The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of Metabolism: NOVEL INSIGHTS INTO DRUG MECHANISMS OF ACTION.
H. I. M. Boshoff, T. G. Myers, B. R. Copp, M. R. McNeil, M. A. Wilson, and C. E. Barry III (2004)
J. Biol. Chem. 279, 40174-40184
   Abstract »    Full Text »    PDF »
Effects of Inorganic Polyphosphate on the Proteolytic and DNA-binding Activities of Lon in Escherichia coli.
K. Nomura, J. Kato, N. Takiguchi, H. Ohtake, and A. Kuroda (2004)
J. Biol. Chem. 279, 34406-34410
   Abstract »    Full Text »    PDF »
Thiamine Triphosphate, a New Signal Required for Optimal Growth of Escherichia coli during Amino Acid Starvation.
B. Lakaye, B. Wirtzfeld, P. Wins, T. Grisar, and L. Bettendorff (2004)
J. Biol. Chem. 279, 17142-17147
   Abstract »    Full Text »    PDF »
PepN is the major aminopeptidase in Escherichia coli: insights on substrate specificity and role during sodium-salicylate-induced stress.
D. Chandu and D. Nandi (2003)
Microbiology 149, 3437-3447
   Abstract »    Full Text »    PDF »
Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells.
L. Wang, C. D. Fraley, J. Faridi, A. Kornberg, and R. A. Roth (2003)
PNAS 100, 11249-11254
   Abstract »    Full Text »    PDF »
Modulation of Mitogenic Activity of Fibroblast Growth Factors by Inorganic Polyphosphate.
T. Shiba, D. Nishimura, Y. Kawazoe, Y. Onodera, K. Tsutsumi, R. Nakamura, and M. Ohshiro (2003)
J. Biol. Chem. 278, 26788-26792
   Abstract »    Full Text »    PDF »
Modification in the ppk Gene of Helicobacterpylori during Single and Multiple Experimental Murine Infections.
S. Ayraud, B. Janvier, L. Salaun, and J.-L. Fauchere (2003)
Infect. Immun. 71, 1733-1739
   Abstract »    Full Text »    PDF »
Global Role for ClpP-Containing Proteases in Stationary-Phase Adaptation of Escherichia coli.
D. Weichart, N. Querfurth, M. Dreger, and R. Hengge-Aronis (2003)
J. Bacteriol. 185, 115-125
   Abstract »    Full Text »    PDF »
Adaptation to famine: A family of stationary-phase genes revealed by microarray analysis.
T. H. Tani, A. Khodursky, R. M. Blumenthal, P. O. Brown, and R. G. Matthews (2002)
PNAS 99, 13471-13476
   Abstract »    Full Text »    PDF »
The Exopolyphosphatase Gene from Sulfolobus solfataricus: Characterization of the First Gene Found To Be Involved in Polyphosphate Metabolism in Archaea.
S. T. Cardona, F. P. Chavez, and C. A. Jerez (2002)
Appl. Envir. Microbiol. 68, 4812-4819
   Abstract »    Full Text »    PDF »
Signal Transduction and Regulatory Mechanisms Involved in Control of the {sigma}S (RpoS) Subunit of RNA Polymerase.
R. Hengge-Aronis (2002)
Microbiol. Mol. Biol. Rev. 66, 373-395
   Abstract »    Full Text »    PDF »
CELL BIOLOGY: Enhanced: Surviving Starvation.
S. Gottesman and M. R. Maurizi (2001)
Science 293, 614-615
   Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882