Bioactivity of metallothionein-3 correlates with its novel beta domain sequence rather than metal binding properties.
Bioactivity of metallothionein-3 correlates with its novel beta domain sequence rather than metal binding properties.
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DOI：
10.1021/bi00014a031
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发表时间：
1995-04
期刊：
影响因子：
2.9
通讯作者：
A. Sewell;L. T. Jensen;Jay C. Erickson;R. Palmiter;D. Winge
中科院分区：
文献类型：
--
作者：
A. Sewell;L. T. Jensen;Jay C. Erickson;R. Palmiter;D. Winge
人类和小鼠金属硫蛋白-3 (MT-3) 分子与 Zn(II)、Cd(II) 或 Cu(I) 表现出与 MT-1 或 MT-2 分子相同的金属结合化学计量，表明 MT-3 由两个包含独立多金属簇的结构域组成。 MT-3 与螯合剂乙二胺四乙酸 (EDTA) 或硫醇试剂二硫代双 (2-硝基苯甲酸) (DTNB) 形成的 Zn(II) 络合物的动力学反应性与 ZnMT-1 的反应性相似。此外，人MT-3的候选α和β结构域肽在Zn(II)络合物的反应性方面与MT-1结构域肽非常相似。人类和小鼠 MT-3 的 Zn(II) 复合物可抑制在阿尔茨海默氏病脑提取物存在下培养的大鼠皮质神经元的存活。抑制活性是 MT-3 同工型所独有的，并且是 N 末端 β 结构域的特性。 32 个残基的 MT-3 β 结构域的抑制活性被 β 结构域内的双突变消除，导致 C-P-C-P 序列转换为 C-S-C-A 或 C-T-C-T。因此，生物活性源自 MT-3 N 端 β 结构域的新颖结构，而不是任何不寻常的金属结合特性。
Human and mouse metallothionein-3 (MT-3) molecules exhibit the same metal binding stoichiometry with Zn(II), Cd(II), or Cu(I) as MT-1 or MT-2 molecules, suggesting that MT-3 consists of two domains enfolding separate polymetallic clusters. The kinetic reactivities of Zn(II) complexes of MT-3 with the chelator ethylenediaminetetraacetic acid (EDTA) or the thiol reagent dithiobis(2-nitrobenzoic acid) (DTNB) resembles the reactivity of ZnMT-1. Furthermore, the candidate alpha and beta domain peptides of human MT-3 are very similar to MT-1 domain peptides in the reactivity of Zn(II) complexes. Zn(II) complexes of human and mouse MT-3 inhibit the survival of rat cortical neurons cultured in the presence of an Alzheimer's disease brain extract. Inhibitory activity is unique to the MT-3 isoform and is a property of the N-terminal beta domain. The inhibitory activity of the 32-residue MT-3 beta domain is abolished by a double mutation within the beta domain resulting in the conversion of the C-P-C-P sequence to either C-S-C-A or C-T-C-T. Thus, the bioactivity arises from a novel structure of the N-terminal beta domain of MT-3 and not any unusual metal-binding properties.