Leszczyszyn Oksana Iryna, White Craig Roy J, Blindauer Claudia Andrea
Department of Chemistry, University of Warwick, Coventry, UK CV4 7AL.
Mol Biosyst. 2010 Sep;6(9):1592-603. doi: 10.1039/c002348e.
The selectivity of proteins involved in metal ion homeostasis is an important part of the puzzle to understand how cells allocate the correct metal ions to the correct proteins. Due to their similar ligand-binding properties, and their frequent co-existence in soils, essential zinc and toxic cadmium are a particularly challenging couple. Thus, minimisation of competition of Cd(2+) for Zn(2+) sites is of crucial importance for organisms that are in direct contact with soil. Amongst these, plants have an especially critical role, due to their importance for nutrition and energy. We have studied an embryo-specific, zinc-binding metallothionein (E(C)) from wheat by nuclear magnetic resonance, electrospray mass spectrometry, site-directed mutagenesis, and molecular modelling. Wheat E(C) exploits differences in affinities of Cys(4) and Cys(2)His(2) sites for Cd(2+) and Zn(2+) to achieve metal-selective protein folding. We propose that this may constitute a novel mechanism to discriminate between essential Zn(2+) and toxic Cd(2+).
参与金属离子稳态的蛋白质的选择性是理解细胞如何将正确的金属离子分配到正确蛋白质这一难题的重要组成部分。由于必需的锌和有毒的镉具有相似的配体结合特性，且它们在土壤中经常共存，因此它们是一对特别具有挑战性的组合。因此，对于直接接触土壤的生物体来说，将镉（2+）对锌（2+）位点的竞争降至最低至关重要。其中，植物由于其对营养和能量的重要性而具有特别关键的作用。我们通过核磁共振、电喷雾质谱、定点诱变和分子建模研究了小麦中一种胚胎特异性的锌结合金属硫蛋白（E(C)）。小麦E(C)利用半胱氨酸（4）和半胱氨酸（2）组氨酸（2）位点对镉（2+）和锌（2+）亲和力的差异来实现金属选择性蛋白质折叠。我们认为这可能构成一种区分必需锌（2+）和有毒镉（2+）的新机制。
