Dept. de Química, Fac. de Ciències, Universitat Autònoma de Barcelona, 08193-Bellaterra, Barcelona, Spain.
Metallomics. 2013 Oct;5(10):1397-410. doi: 10.1039/c3mt00123g.
Metallothioneins (MTs) constitute a universal family of polymorphic, ubiquitous small Cys-rich metal-binding polypeptides that in mammals are represented by four highly similar isoforms (MT1 to MT4). MT1 and MT2 have generally been considered as equivalent proteins, so that they are commonly referred to as MT1/MT2. However, transcription data have suggested a differential behavior for both gene products. In the present study, the metal binding abilities of mouse MT2 (mMT2) with divalent (Zn(II) and Cd(II)) and monovalent (Cu(I)) ions were analyzed and compared to those of the mouse MT1 (mMT1) isoform, previously determined using the same methodological approach. The comprehensive consideration of all the results obtained in this work experimentally demonstrates that the mMT2 isoform exhibits metal ion binding abilities distinct from those of mMT1, with a clear preference for Zn(II) coordination, if compared to Cu(I) or even to Cd(II). This is in full agreement with the gene expression regulation pattern for the MT1 and MT2 genes, as well as with the hypothesized preferential role of mMT2 in Zn(II) homeostasis mechanisms, while MT1, possibly differentiated from a most recent duplication event in the mammalian MT gene cluster, would have evolved to detoxify Cd(II), and probably other divalent metal ions.
金属硫蛋白（MTs）构成了一个普遍存在的多态性、无处不在的小 Cys 丰富的金属结合多肽家族，在哺乳动物中由四个高度相似的同工型（MT1 到 MT4）组成。MT1 和 MT2 通常被认为是等效的蛋白质，因此它们通常被称为 MT1/MT2。然而，转录数据表明这两种基因产物的行为存在差异。在本研究中，使用相同的方法学方法，分析并比较了二价（Zn(II) 和 Cd(II)）和单价（Cu(I)）离子与鼠 MT1（mMT1）同工型的结合能力。综合考虑本工作中获得的所有实验结果，实验证明 mMT2 同工型表现出与 mMT1 不同的金属离子结合能力，如果与 Cu(I) 甚至 Cd(II) 相比，对 Zn(II) 配位有明显的偏好。这与 MT1 和 MT2 基因的基因表达调控模式完全一致，也与 mMT2 在 Zn(II) 稳态机制中优先发挥作用的假设一致，而 MT1 可能是从哺乳动物 MT 基因簇最近的一次重复事件中分化出来的，其进化可能是为了解毒 Cd(II)，可能还有其他二价金属离子。
