Inorganic Stressors of Ubiquitin

被引：25

作者：

Arena, Giuseppe ^{[1
]}

Bellia, Francesco ^{[2
]}

Frasca, Giuseppina ^{[2
]}

Grasso, Giulia ^{[2
]}

Lanza, Valeria ^{[2
]}

Rizzarelli, Enrico ^{[1
,2
]}

Tabbi, Giovanni ^{[2
]}

Zito, Valeria ^{[2
]}

Milardi, Danilo ^{[2
]}

机构：

[1] Univ Catania, Dipartimento Sci Chim, I-95125 Catania, Italy

[2] CNR, Ist Biostrutture & Bioimmagini UOS CT, I-95125 Catania, Italy

来源：

INORGANIC CHEMISTRY | 2013年 / 52卷 / 16期

关键词：

COPPER(II) COMPLEXES; POLYUBIQUITIN CHAINS; PARKINSONS-DISEASE; PROTEASOME PATHWAY; STRUCTURAL BASIS; PRION PROTEIN; COORDINATION; SYSTEM; THERMODYNAMICS; AGGREGATION;

D O I：

10.1021/ic401276x

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

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 dose relationship between metal dyshomeostasis and abnormal protein degradative pathways in the upstream events, triggering neurodegeneration.

引用

页码：9567 / 9573

页数：7

共 53 条

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