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Inorganic stressors of ubiquitin
- Source :
- Inorganic chemistry 52 (2013): 9567–9573. doi:10.1021/ic401276x, info:cnr-pdr/source/autori:Arena, Giuseppe; Bellia, Francesco; Frasca, Giuseppina; Grasso, Giulia; Lanza, Valeria; Rizzarelli, Enrico; Tabbi, Giovanni; Zito, Valeria; Milardi, Danilo/titolo:Inorganic Stressors of Ubiquitin/doi:10.1021%2Fic401276x/rivista:Inorganic chemistry/anno:2013/pagina_da:9567/pagina_a:9573/intervallo_pagine:9567–9573/volume:52
- Publication Year :
- 2013
-
Abstract
- Many neurodegenerative proteinopathies are characterized by ubiquitin (Ub)-containing intraneuronal inclusion bodies. Recent reports have shown that Ub is able to bind Cu(II) and Zn(II), the dyshomeostasis of which is a hallmark of neurodegeneration. Here we use complementary techniques like potentiometry, circular dichroism-visible, and electron spin resonance to unveil the Ub/metal species that form, at neutral pH, their binding constants and structural features. Next, we show that both Zn(II) and Cu(II) ions hinder the interactions between Ub and Ub-conjugating E2 enzymes and inhibit significantly both Lys48 and Lys63 self-polyubiquitination reactions in a cell-free medium. The effects of Zn(II) and Cu(II) on Lys63 and Lys48 polyUb chain synthesis are compatible with the hypothesis that metal binding to His68 modifies the Ile44 hydrophobic patch of Ub and makes the protein less available for polyUb. These findings contribute to further arguments for a close relationship between metal dyshomeostasis and abnormal protein degradative pathways in the upstream events, triggering neurodegeneration.
- Subjects :
- Models, Molecular
neurodegenration
Stereochemistry
Inclusion bodies
law.invention
Inorganic Chemistry
Metal
Ubiquitin
metal dyshomeostasis
law
medicine
Homeostasis
Physical and Theoretical Chemistry
Neutral ph
Electron paramagnetic resonance
chemistry.chemical_classification
biology
Lysine
Neurodegeneration
Ubiquitination
Neurodegenerative Diseases
Hydrogen-Ion Concentration
medicine.disease
Zinc
Enzyme
chemistry
Close relationship
visual_art
Ubiquitin-Conjugating Enzymes
visual_art.visual_art_medium
biology.protein
Copper
Subjects
Details
- ISSN :
- 1520510X
- Volume :
- 52
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- Inorganic chemistry
- Accession number :
- edsair.doi.dedup.....6760b46b73bcca78e77636c4f37b60fc