The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation - PubMed (original) (raw)

The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation

C C Philpott et al. Proc Natl Acad Sci U S A. 1994.

Abstract

The iron-responsive element binding protein/cytosolic aconitase functions as either an RNA binding protein that regulates the uptake, sequestration, and utilization of iron or an enzyme that interconverts citrate and isocitrate. These mutually exclusive functions are regulated by changes in cellular iron levels. By site-directed mutagenesis we show that (i) ligation of a [4Fe-4S] cluster is necessary to inactivate RNA binding and activate enzyme function in vivo, (ii) three of four arginine residues of the aconitase active site participate in RNA binding, and (iii) aconitase activity is not required for iron-mediated regulation of RNA binding.

PubMed Disclaimer

Similar articles

• The iron-responsive element-binding protein: localization of the RNA-binding site to the aconitase active-site cleft.
  Basilion JP, Rouault TA, Massinople CM, Klausner RD, Burgess WH. Basilion JP, et al. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):574-8. doi: 10.1073/pnas.91.2.574. Proc Natl Acad Sci U S A. 1994. PMID: 8290565 Free PMC article.
• Novel role of phosphorylation in Fe-S cluster stability revealed by phosphomimetic mutations at Ser-138 of iron regulatory protein 1.
  Brown NM, Anderson SA, Steffen DW, Carpenter TB, Kennedy MC, Walden WE, Eisenstein RS. Brown NM, et al. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15235-40. doi: 10.1073/pnas.95.26.15235. Proc Natl Acad Sci U S A. 1998. PMID: 9860952 Free PMC article.
• Mutational analysis of the [4Fe-4S]-cluster converting iron regulatory factor from its RNA-binding form to cytoplasmic aconitase.
  Hirling H, Henderson BR, Kühn LC. Hirling H, et al. EMBO J. 1994 Jan 15;13(2):453-61. doi: 10.1002/j.1460-2075.1994.tb06280.x. EMBO J. 1994. PMID: 7508861 Free PMC article.
• An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein.
  Rouault TA, Haile DJ, Downey WE, Philpott CC, Tang C, Samaniego F, Chin J, Paul I, Orloff D, Harford JB, et al. Rouault TA, et al. Biometals. 1992 Autumn;5(3):131-40. doi: 10.1007/BF01061319. Biometals. 1992. PMID: 1421965 Review.
• Iron-sulphur clusters as genetic regulatory switches: the bifunctional iron regulatory protein-1.
  Paraskeva E, Hentze MW. Paraskeva E, et al. FEBS Lett. 1996 Jun 24;389(1):40-3. doi: 10.1016/0014-5793(96)00574-1. FEBS Lett. 1996. PMID: 8682202 Review.

Cited by

• FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells.
  Lin H, Lin S, Shi L, Xu G, Lin M, Li S, Chen J, Li Z, Nakazibwe C, Xiao Y, Li X, Pan X, Wang C. Lin H, et al. Commun Biol. 2024 Aug 17;7(1):1011. doi: 10.1038/s42003-024-06704-6. Commun Biol. 2024. PMID: 39154074 Free PMC article.
• Mechanisms and regulations of ferroptosis.
  Zhang XD, Liu ZY, Wang MS, Guo YX, Wang XK, Luo K, Huang S, Li RF. Zhang XD, et al. Front Immunol. 2023 Oct 6;14:1269451. doi: 10.3389/fimmu.2023.1269451. eCollection 2023. Front Immunol. 2023. PMID: 37868994 Free PMC article. Review.
• An alternative vaccine target for bovine Anaplasmosis based on enolase, a moonlighting protein.
  Quiroz-Castañeda RE, Aguilar-Díaz H, Amaro-Estrada I. Quiroz-Castañeda RE, et al. Front Vet Sci. 2023 Sep 22;10:1225873. doi: 10.3389/fvets.2023.1225873. eCollection 2023. Front Vet Sci. 2023. PMID: 37808115 Free PMC article.
• Iron regulatory protein 1 promotes ferroptosis by sustaining cellular iron homeostasis in melanoma.
  Yao F, Cui X, Zhang Y, Bei Z, Wang H, Zhao D, Wang H, Yang Y. Yao F, et al. Oncol Lett. 2021 Sep;22(3):657. doi: 10.3892/ol.2021.12918. Epub 2021 Jul 12. Oncol Lett. 2021. PMID: 34386079 Free PMC article.
• Defects in the rice aconitase-encoding OsACO1 gene alter iron homeostasis.
  Senoura T, Kobayashi T, An G, Nakanishi H, Nishizawa NK. Senoura T, et al. Plant Mol Biol. 2020 Dec;104(6):629-645. doi: 10.1007/s11103-020-01065-0. Epub 2020 Sep 9. Plant Mol Biol. 2020. PMID: 32909184

References

1. 1. Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 - PubMed
2. 1. EMBO J. 1994 Jan 15;13(2):453-61 - PubMed
3. 1. EMBO J. 1988 Apr;7(4):913-8 - PubMed
4. 1. Proc Natl Acad Sci U S A. 1989 May;86(10):3639-43 - PubMed
5. 1. J Biol Chem. 1989 Jul 5;264(19):11204-10 - PubMed

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central

• Other Literature Sources

  • The Lens - Patent Citations

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology
  • GlyGen glycoinformatics resource