Iron-Dependent RNA-Binding Activity of Mycobacterium tuberculosis Aconitase
Open accessAbstract
Cellular iron levels are closely monitored by iron regulatory and sensor proteins of Mycobacterium tuberculosis for survival inside macrophages. One such class of proteins systematically studied in eukaryotes and reported in a few prokaryotes are the iron-responsive proteins (IRPs). These IRPs bind to iron-responsive elements (IREs) present at untranslated regions (UTRs) of mRNAs and are responsible for posttranscriptional regulation of the expression of proteins involved in iron homeostasis. Amino acid sequence analysis of M. tuberculosis aconitase (Acn), a tricarboxylic acid (TCA) cycle enzyme, showed the presence of the conserved residues of the IRP class of proteins. We demonstrate that M. tuberculosis Acn is bifunctional. It is a monomeric protein that is enzymatically active in converting isocitrate to cis -aconitate at a broad pH range of 7 to 10 (optimum, pH 8). As evident from gel retardation assays, M. tuberculosis Acn also behaves like an IRP by binding to known mammalian IRE-like sequences and to predicted IRE-like sequences present at the 3′ UTR of thioredoxin ( trxC ) and the 5′ UTR of the iron-dependent repressor and activator ( ideR ) of M. tuberculosis. M. tuberculosis Acn when reactivated with Fe 2+ functions as a TCA cycle enzyme, but upon iron depletion by a specific iron chelator, it behaves like an IRP, binding to the selected IREs in vitro. Since iron is required for the Acn activity and inhibits the RNA-binding activity of Acn, the two activities of M. tuberculosis Acn are mutually exclusive. Our results demonstrate the bifunctional nature of M. tuberculosis Acn, pointing to its likely role in iron homeostasis.
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Functional IRPs have been detected within M. tuberculosis.
“because functional IRPs have been detected within these bacteria (192).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [192]
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Cites
Iron-sulfur clusters: nature's modular, multipurpose structures
Beinert, H., Holm, R. H., & Münck, E. (1997) · Science · doi:10.1126/science.277.5326.653 · Cited by 1,944 · see citing works
Betts, J. C., Lukey, P. T., Robb, L. C., McAdam, R. A., & Duncan, K. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02779.x · Cited by 1,395 · see citing works
The role of iron regulatory proteins in mammalian iron homeostasis and disease
Rouault, T. A. (2006) · Nature Chemical Biology · doi:10.1038/nchembio807 · Cited by 1,055 · see citing works
Aconitase as iron–sulfur protein, enzyme, and iron-regulatory protein
Beinert, H., Kennedy, M. C., & Stout, C. D. (1996) · Chemical Reviews · doi:10.1021/cr950040z · Cited by 606 · cited 1× · see citing works
“The iron-sulfur clusters of these proteins not only participate in electron transport during reversible isomerization of citrate and isocitrate in citric acid cycle (7) but also serve as iron and oxygen sensors of the cell (6, 23).”
BackgroundRapid responses to oxidative stress mediated by iron regulatory protein.
Pantopoulos, K., & Hentze, M. W. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07291.x · Cited by 328 · see citing works
Aconitase, a two‐faced protein: enzyme and iron regulatory factor 1 2
Beinert, H., & Kennedy, M. C. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.15.8262329 · Cited by 277 · see citing works
Haile, D. J., Rouault, T. A., Tang, C., Chin, J., Harford, J. B., & Klausner, R. D. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7536 · Cited by 270 · see citing works
Koeller, D. M., Casey, J. L., Hentze, M. W., Gerhardt, E. M., Chan, L.-N. L., Klausner, R. D., & Harford, J. B. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.10.3574 · Cited by 242 · see citing works
Regulation of Iron Metabolism in Eukaryotes
Rouault, T. A., & Klausner, R. D. (1997) · Current topics in cellular regulation · doi:10.1016/s0070-2137(97)80001-5 · Cited by 239 · see citing works
Contrasting Sensitivities of Escherichia coli Aconitases A and B to Oxidation and Iron Depletion
Varghese, S., Tang, Y., & Imlay, J. A. (2002) · Journal of Bacteriology · doi:10.1128/jb.185.1.221-230.2003 · Cited by 215 · see citing works
Tian, J., Bryk, R., Itoh, M., Suematsu, M., & Nathan, C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501605102 · Cited by 200 · see citing works
Gray, N. K., Pantopoulos, K., Dandekar, T., Ackrell, B. A. C., & Hentze, M. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4925 · Cited by 187 · see citing works
Bacillus subtilis aconitase is an RNA-binding protein
Amaro, C. A., & Sonenshein, A. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.10412 · Cited by 159 · see citing works
Direct evidence for mRNA binding and post-transcriptional regulation by Escherichia coli aconitases
Tang, Y., & Guest, J. R. (1999) · Microbiology · doi:10.1099/00221287-145-11-3069 · Cited by 158 · see citing works
Differences in the RNA binding sites of iron regulatory proteins and potential target diversity.
Butt, J., Kim, H. Y., Basilion, J. P., Cohen, S., Iwaï, K., Philpott, C. C., Altschul, S. F., Klausner, R. D., & Rouault, T. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.4345 · Cited by 139 · see citing works
Wong, D. K., Lee, B., Horwitz, M. A., & Gibson, B. W. (1999) · Infection and Immunity · doi:10.1128/iai.67.1.327-336.1999 · Cited by 132 · see citing works
PPE Antigen Rv2430c of Mycobacterium tuberculosis Induces a Strong B-Cell Response
Choudhary, R. K., Mukhopadhyay, S., Chakhaiyar, P., Sharma, N., Murthy, K. J. R., Katoch, V. M., & Hasnain, S. E. (2003) · Infection and Immunity · doi:10.1128/iai.71.11.6338-6343.2003 · Cited by 132 · see citing works
Self-citationSiddiqi, N., Pathak, N., Banerjee, S., Ahmed, N., Katoch, V. M., Hasnain, S. E., & Das, R. (2004) · Infection · doi:10.1007/s15010-004-3097-x · Cited by 123 · see citing works
Self-citationMetabolic enzymes that bind RNA: yet another level of cellular regulatory network?
Cieśla, J. (2006) · Acta Biochimica Polonica · doi:10.18388/abp.2006_3360 · Cited by 106 · see citing works
Biochemical and spectroscopic characterization of Escherichia coli aconitases (AcnA and AcnB)
JORDAN, P. A., Tang, Y., Bradbury, A. J., THOMSON, A. J., & Guest, J. R. (1999) · Biochemical Journal · doi:10.1042/bj3440739 · Cited by 97 · see citing works
Chakhaiyar, P., Nagalakshmi, Y., Aruna, B., Murthy, K. J. R., Katoch, V. M., & Hasnain, S. E. (2004) · The Journal of Infectious Diseases · doi:10.1086/423938 · Cited by 94 · see citing works
Self-citationCrystal Structures of Aconitase with Trans-aconitate and Nitrocitrate Bound
Lauble, H., Kennedy, M. C., Beinert, H., & Stout, C. D. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1246 · Cited by 93 · see citing works
Wilson, T. J., Bertrand, N., Tang, J. ‐., Feng, J., Pan, M.-Y., Barber, C. E., Dow, J. M., & Daniels, M. J. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00852.x · Cited by 92 · see citing works
Baughn, A. D., & Malamy, M. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052710199 · Cited by 90 · see citing works
Cytosolic Aconitase and Ferritin Are Regulated by Iron inCaenorhabditis elegans
Gourley, B. L., Parker, S. B., Jones, B. J., Zumbrennen‐Bullough, K. B., & Leibold, E. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210333200 · Cited by 88 · see citing works
Koeller, K. M. (1989) · Medical Entomology and Zoology · Cited by 72 · see citing works
Banerjee, S., Nandyala, A., Podili, R., Katoch, V. M., Murthy, K. J. R., & Hasnain, S. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404347101 · Cited by 63 · see citing works
Self-citationCHAUHAN, R., & Mande, S. C. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3540209 · Cited by 60 · see citing works
Post-Transcriptional Regulation of Human Iron Metabolism by Iron Regulatory Proteins
Rouault, T. A. (2002) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2002.0571 · Cited by 58 · see citing works
Iron Regulatory Protein 2 as Iron Sensor
Kang, D., Jeong, J., Drake, S. K., Wehr, N. B., Rouault, T. A., & Levine, R. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300616200 · Cited by 57 · see citing works
Iron‐regulatory protein‐1 (IRP‐1) is highly conserved in two invertebrate species
Muckenthaler, M. U., Gunkel, N., Frishman, D., et al. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2540230.x · Cited by 55 · see citing works
Somerville, G. A., Mikoryak, C., & Reitzer, L. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.4.1072-1078.1999 · Cited by 52 · see citing works
Method for Enhancing Solubility of the Expressed Recombinant Proteins in Escherichia Coli
Ghosh, S., Rasheedi, S., Rahim, S. S., et al. (2004) · BioTechniques · doi:10.2144/04373st07 · Cited by 48 · see citing works
Conservation of Aconitase Residues Revealed by Multiple Sequence Analysis
Frishman, D., & Hentze, M. W. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.0197u.x · Cited by 48 · see citing works
Redox control of iron regulatory proteins
Fillebeen, C., & Pantopoulos, K. (2002) · Redox Report · doi:10.1179/135100002125000136 · Cited by 44 · see citing works
From bacteria to mitochondria: Aconitase yields surprises
Walden, W. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082108799 · Cited by 43 · see citing works
CHAUHAN, R., & Mande, S. C. (2001) · Biochemical Journal · doi:10.1042/bj3540209 · Cited by 38 · see citing works
Cloning and molecular characterization of two mosquito iron regulatory proteins
Zhang, D., Dimopoulos, G., Wolf, A. S., Miñana, B., Kafatos, F. C., & Winzerling, J. J. (2002) · Insect Biochemistry and Molecular Biology · doi:10.1016/s0965-1748(01)00138-2 · Cited by 35 · see citing works
Banerjee, S., Nandyala, A., Podili, R., Katoch, V. M., & Hasnain, S. E. (2005) · BMC Biochemistry · doi:10.1186/1471-2091-6-20 · Cited by 31 · see citing works
Self-citationGegout, V., Schlegl, J., Schläger, B., Hentze, M. W., Reinbolt, J., Ehresmann, B., Ehresmann, C., & Romby, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.21.15052 · Cited by 25 · see citing works
Iron-activated iron uptake: A positive feedback loop mediated by iron regulatory protein 1
Núñez, M. T., Núñez‐Millacura, C., Tapia, V., Muñoz, P., Mazariegos, D. I., Arredondo, M., Muñoz, P., Mura, C. V., & Maccioni, R. B. (2003) · BioMetals · doi:10.1023/a:1020743405347 · Cited by 23 · see citing works
Defining the Mandate of Tuberculosis Research in a Postgenomic Era
Chakhaiyar, P., & Hasnain, S. E. (2004) · Medical Principles and Practice · doi:10.1159/000078312 · Cited by 20 · see citing works
Self-citation
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Research works printed but not linked: 1
- [1]1. Ale ´n, C., and A. L. Sonenshein. 1999. Bacillus subtilis aconitase is an RNAbinding protein. Proc. Natl. Acad. Sci. USA 96: 10412-10417.
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Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989 · see citing works
Olakanmi, O., Kesavalu, B., Pasula, R., Abdalla, M. Y., Schlesinger, L. S., & Britigan, B. E. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01543-13 · Cited by 70 · see citing works
Iron acquisition, assimilation and regulation in mycobacteria
Banerjee, S., Farhana, A., Ehtesham, N. Z., & Hasnain, S. E. (2011) · Infection, Genetics and Evolution · doi:10.1016/j.meegid.2011.02.016 · Cited by 57 · see citing works
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- Authors
- Banerjee, S., Nandyala, A. K., Raviprasad, P., Ahmed, N., & Hasnain, S. E.
- Affiliations
- University of Hyderabad (IN)
- Centre for DNA Fingerprinting and Diagnostics (IN)
- Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, 500076, India
- Jawaharlal Nehru Centre for Advanced Scientific Research (IN)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2007-06
- Volume
- 189
- Issue
- 11
- Pages
- 4046-4052
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC1913386
- OpenAlex
- W2123356497
- Cited by
- 98
- References
- 42
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 9 · 2014: 7 · 2013: 9 · 2012: 4
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India
- Centre for DNA Fingerprinting and Diagnostics
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Mycobacterium tuberculosis, aconitase, iron regulatory element, RNA-binding activity, iron homeostasis, post-transcriptional regulation, bifunctional protein, TCA cycle, thioredoxin, IdeR, iron depletion, iron chelation, macrophage survival
- MeSH terms
- Aconitate Hydratase, Bacterial Proteins, Chromatography, Gel, Hydrogen-Ion Concentration, Iron, Mycobacterium tuberculosis, Protein Binding, Recombinant Fusion Proteins, RNA, Substrate Specificity, Polymerase Chain Reaction, Open Reading Frames, RNA-Binding Proteins, Dimerization, Electrophoretic Mobility Shift Assay, Iron-Regulatory Proteins
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