Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins.
Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins.
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DOI：
10.1016/j.bbamcr.2011.01.017
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Grabarek Z
中科院分区：
文献类型：
--
作者：
Grabarek Z
Ca2+ 结合螺旋-环-螺旋结构基序称为 EF-hand，是作为细胞内 Ca2+ 受体发挥作用的一大蛋白家族的常见构建块。在化学性质相似的二价阳离子 Mg2+ 过量约 1000 倍的情况下，这些蛋白质对微摩尔浓度的 Ca2+ 产生特异性反应。细胞内游离 Mg2+ 浓度严格控制在 0.5–1.0 mM 的狭窄范围内，在静息 Ca2+ 水平下，该浓度足以完全或部分饱和许多 EF-hand 蛋白的 Ca2+ 结合位点。因此，为了传递 Ca2+ 信号，EF 手蛋白对 Ca2+ 的反应必须与对 Mg2+ 的反应不同。在本综述中，根据最近提出的两步 Ca2+ 结合机制，考虑并解释了 Mg2+ 与 EF-hand 蛋白结合的结构方面（Grabarek, Z., J. Mol. Biol. 346,1351,2005）。据认为，由于双 EF 手域结构所施加的立体化学限制，较小的 Mg2+ 离子不能以与 Ca2+ 相同的方式与 EF 手的配体结合，并且默认稳定 EF 手的 apo 样构象。据认为，Mg2+ 通过稳定一些 EF-hand 蛋白的关闭状态，从而促进在静息 Ca2+ 水平下关闭各自的靶酶，从而在细胞过程的 Ca2+ 依赖性调节中发挥积极作用。因此，一些由 Mg2+ 缺乏引起的病理状况可能与潜在的 Ca2+ 调节细胞过程的过度激活有关。
The Ca2+-binding helix-loop-helix structural motif called EF-hand is a common building block of a large family of proteins that function as intracellular Ca2+ receptors. These proteins respond specifically to micromolar concentrations of Ca2+ in the presence of ~1000 fold excess of the chemically similar divalent cation Mg2+. The intracellular free Mg2+ concentration is tightly controlled in a narrow range of 0.5–1.0 mM, which at the resting Ca2+ levels is sufficient to fully or partially saturate the Ca2+ binding sites of many EF-hand proteins. Thus, to convey Ca2+ signals, EF-hand proteins must respond differently to Ca2+ than to Mg2+. In this review the structural aspects of Mg2+ binding to EF-hand proteins are considered and interpreted in light of the recently proposed two-step Ca2+-binding mechanism (Grabarek, Z., J. Mol. Biol. 346,1351,2005). It is proposed that, due to stereochemical constraints imposed by the two-EF-hand domain structure, the smaller Mg2+ ion cannot engage the ligands of an EF-hand in the same way as Ca2+ and defaults to stabilizing the apo-like conformation of the EF-hand. It is proposed that Mg2+ plays an active role in the Ca2+-dependent regulation of cellular processes by stabilizing the off state of some EF-hand proteins, thereby facilitating switching off their respective target enzymes at the resting Ca2+ levels. Therefore, some pathological conditions attributed to Mg2+ deficiency might be related to excessive activation of underlying Ca2+-regulated cellular processes.
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影响因子：
64.8
作者：
Drum, CL;Yan, SZ;Tang, WJ
通讯作者：
Tang, WJ
影响因子：
4.8
作者：
DASILVA, ACR;KENDRICKJONES, J;REINACH, FC
通讯作者：
REINACH, FC
影响因子：
11.4
作者：
Agianian, B;Krzic, U;Bullard, B
通讯作者：
Bullard, B
影响因子：
--
作者：
BONDI, A
通讯作者：
BONDI, A
DOI：
10.1107/s0567740881005037
发表时间：
1981-01-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE
影响因子：
--
作者：
EINSPAHR, H;BUGG, CE
通讯作者：
BUGG, CE