Denesyuk Alexander I, Permyakov Sergei E, Johnson Mark S, Permyakov Eugene A, Denessiouk Konstantin
Faculty of Science and Engineering, Åbo Akademi University, Turku 20500, Finland; Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino 142290, Russia.
Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino 142290, Russia.
Biochem Biophys Res Commun. 2017 Feb 12;483(3):958-963. doi: 10.1016/j.bbrc.2017.01.040. Epub 2017 Jan 12.
Metal ions can regulate various cell processes being first, second or third messengers, and some of them, especially transition metal ions, take part in catalysis in many enzymes. As an intracellular ion, Ca is involved in many cellular functions from fertilization and contraction, cell differentiation and proliferation, to apoptosis and cancer. Here, we have identified and described two novel calcium recognition environments in proteins: the calcium blade zone and the EF-hand zone, common to 12 and 8 different protein families, respectively. Each of the two environments contains three distinct structural elements: (a) the well-known characteristic Dx[DN]xDG motif; (b) an adjacent structurally identical segment, which binds metal ion in the same way between the calcium blade zone and the EF-hand zone; and (c) the following structurally variable segment, which distinguishes the calcium blade zone from the EF-hand zone. Both zones have sequence insertions between the last residue of the zone and calcium-binding residues in positions V or VI. The long insertion often connects the active and the calcium-binding sites in proteins. Using the structurally identical segments as an anchor, we were able to construct the classical calmodulin type EF-hand calcium-binding site out of two different calcium-binding motifs from two unrelated proteins.
金属离子作为第一、第二或第三信使可调节各种细胞过程，其中一些金属离子，尤其是过渡金属离子，在许多酶中参与催化作用。作为一种细胞内离子，钙参与从受精、收缩、细胞分化和增殖到细胞凋亡和癌症等许多细胞功能。在此，我们在蛋白质中鉴定并描述了两种新的钙识别环境：钙叶片区和EF手型区，它们分别存在于12个和8个不同的蛋白质家族中。这两种环境中的每一种都包含三个不同的结构元件：(a) 众所周知的特征性Dx[DN]xDG基序；(b) 一个相邻的结构相同片段，其在钙叶片区和EF手型区之间以相同方式结合金属离子；以及(c) 随后的结构可变片段，它将钙叶片区与EF手型区分开。这两个区域在该区域的最后一个残基与V或VI位的钙结合残基之间都有序列插入。长插入通常连接蛋白质中的活性位点和钙结合位点。以结构相同的片段为锚，我们能够利用来自两种不相关蛋白质的两种不同钙结合基序构建出经典的钙调蛋白型EF手型钙结合位点。
