Isolation, primary structures and metal binding properties of neuronal growth inhibitory factor (GIF) from bovine and equine brain.
Abstract: Human neuronal growth inhibitory factor (GIF) impairs the survival of cultured neurons and is deficient in the brains of Alzheimer's disease victims. We have isolated and sequenced analogous proteins from bovine and equine brain. By comparing their primary structures with those of human, mouse and rat GIFs, a consensus GIF sequence was obtained. Although this exhibits ca. 65% similarity with primary structures of mammalian metallothioneins (MTs), some significant differences are expected in the content of helix and turn secondary structures. In contrast to MTs, which usually bind 7 Zn(II) ions, human, bovine and equine GIFs contain 1-4 Cu(I) and 3-5 Zn(II) ions in species-specific ratios. The observed Cu(I) phosphorescence (lambda max, 550-590 nm; tau, 100 microseconds at 77 K) indicates the presence of the cuprous ion. Both bovine Cu1Cd5- and the equine Cu3Cd3-GIF derivatives (Cd replacing Zn) exhibit cadmium-dependent absorption and CD features between 220-260 nm characteristic of Cd-thiolate clusters similar to those in Cd-MTs.
Publication Date: 1994-05-30 PubMed ID: 8200454DOI: 10.1016/0014-5793(94)00452-8Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research explores the isolation, structure, and metal binding properties of neuronal growth inhibitory factor (GIF) from cow and horse brains, comparing them to human, mouse, and rat GIFs. The findings suggest that the structure shares similarities with mammalian metallothioneins, but also has key differences. In particular, they bind to copper and zinc ions at different species-specific ratios.
Isolation and Sequencing of GIF from Bovine and Equine Brains
- The researchers isolated and sequenced proteins identical to the human neuronal growth inhibitory factor (GIF) from cow (bovine) and horse (equine) brains. This protein is known to affect the survival of neurons negatively and its deficiency links to Alzheimer’s disease.
- The primary structures of these proteins were compared with those of human, mouse, and rat GIFs, generating a consensus GIF sequence.
Comparison with Mammalian Metallothioneins
- The consensus GIF sequence shared around 65% similarity with the primary structures of mammalian metallothioneins (MTs), proteins that regulate metal ions in cells.
- However, researchers expected significant differences in the content of helix and turn secondary structures, integral elements of a protein’s spatial structure.
Different Metal Binding Properties
- In contrast to MTs, which usually bind with seven zinc ions, human, bovine, and equine GIFs bind with one to four copper ions and three to five zinc ions. The exact ratios were specific to each species.
- The presence of the cuprous ion in these GIFs was confirmed by observed copper phosphorescence.
Characteristics of Bovine and Equine GIF Derivatives
- Both bovine and equine GIFs substitute cadmium for zinc, creating derivatives Cu1Cd5-GIF and Cu3Cd3-GIF, respectively.
- These derivatives demonstrated cadmium-dependent absorption and circular dichroism features between 220-260 nm. This suggested the formation of cadmium-thiolate clusters, similar to those in Cd-MTs.
Cite This Article
APA
Pountney DL, Fundel SM, Faller P, Birchler NE, Hunziker P, Vasák M.
(1994).
Isolation, primary structures and metal binding properties of neuronal growth inhibitory factor (GIF) from bovine and equine brain.
FEBS Lett, 345(2-3), 193-197.
https://doi.org/10.1016/0014-5793(94)00452-8 Publication
Researcher Affiliations
- Biochemisches Institut, Universität Zürich, Switzerland.
MeSH Terms
- Amino Acid Sequence
- Animals
- Brain / metabolism
- Cadmium / metabolism
- Cattle
- Cells, Cultured
- Chromatography, Gel
- Consensus Sequence
- Copper / metabolism
- Growth Inhibitors / chemistry
- Growth Inhibitors / isolation & purification
- Growth Inhibitors / metabolism
- Horses
- Humans
- Metallothionein 3
- Metals / metabolism
- Molecular Sequence Data
- Nerve Tissue Proteins / chemistry
- Nerve Tissue Proteins / isolation & purification
- Nerve Tissue Proteins / metabolism
- Neurons / metabolism
- Sequence Homology, Amino Acid
- Spectrophotometry, Ultraviolet
- Zinc / metabolism
Citations
This article has been cited 9 times.- Peris-Díaz MD, Wu S, Mosna K, Liggett E, Barkhanskiy A, Orzeł A, Barran P, Krężel A. Structural Characterization of Cu(I)/Zn(II)-metallothionein-3 by Ion Mobility Mass Spectrometry and Top-Down Mass Spectrometry. Anal Chem 2023 Jul 25;95(29):10966-10974.
- Mehlenbacher MR, Elsiesy R, Lakha R, Villones RLE, Orman M, Vizcarra CL, Meloni G, Wilcox DE, Austin RN. Metal binding and interdomain thermodynamics of mammalian metallothionein-3: enthalpically favoured Cu(+) supplants entropically favoured Zn(2+) to form Cu(4) (+) clusters under physiological conditions. Chem Sci 2022 May 11;13(18):5289-5304.
- Calvo JS, Lopez VM, Meloni G. Non-coordinative metal selectivity bias in human metallothioneins metal-thiolate clusters. Metallomics 2018 Dec 12;10(12):1777-1791.
- Hidalgo J. Metallothioneins and brain injury: What transgenic mice tell us. Environ Health Prev Med 2004 May;9(3):87-94.
- Pountney DL, Dickson TC, Power JH, Vickers JC, West AJ, Gai WP. Association of metallothionein-III with oligodendroglial cytoplasmic inclusions in multiple system atrophy. Neurotox Res 2011 Jan;19(1):115-22.
- Chung RS, Holloway AF, Eckhardt BL, Harris JA, Vickers JC, Chuah MI, West AK. Sheep have an unusual variant of the brain-specific metallothionein, metallothionein-III. Biochem J 2002 Jul 1;365(Pt 1):323-8.
- Hozumi I, Inuzuka T, Tsuji S. Brain injury and growth inhibitory factor (GIF)--a minireview. Neurochem Res 1998 Mar;23(3):319-28.
- Mosna K, Orzeł A, Tracz M, Wu S, Krężel A. Modification of human metallothioneins by garlic organosulfur compounds, allicin and ajoene: direct effect on zinc homeostasis with relevance to immune regulation. Biometals 2025 Oct;38(5):1513-1533.
- Peris-Díaz MD, Orzeł A, Wu S, Mosna K, Barran PE, Krężel A. Combining Native Mass Spectrometry and Proteomics to Differentiate and Map the Metalloform Landscape in Metallothioneins. J Proteome Res 2024 Aug 2;23(8):3626-3637.
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