X-ray structures of magnesium and manganese complexes with the N-terminal domain of calmodulin: insights into the mechanism and specificity of metal ion binding to an EF-hand.
X-ray structures of magnesium and manganese complexes with the N-terminal domain of calmodulin: insights into the mechanism and specificity of metal ion binding to an EF-hand.
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具有钙调蛋白 N 末端结构域的镁和锰复合物的 X 射线结构：深入了解金属离子与 EF 手结合的机制和特异性。
DOI：
10.1021/bi300698h
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发表时间：
2012-08-07
期刊：
影响因子：
2.9
通讯作者：
Grabarek Z
中科院分区：
文献类型：
--
作者：
Senguen FT;Grabarek Z
钙调素（CaM）是EF-hand超家族的成员之一，在细胞内Mg ~（2+）浓度约为1000× 1000时，对微摩尔浓度的Ca ~（2+）产生特异性反应，调节细胞功能的许多方面。为了解释金属离子结合特异性的结构基础，我们已经解决了与Mg ~（2+），Mn ~（2+）和Zn ~（2+）的复合物中的钙调蛋白（N-CaM）的N-末端结构域的X-射线结构。与Ca 2+诱导CaM结构域开放相反，八面体配位的Mg 2+和Mn 2+稳定了封闭结构域的apo样构象，而四面体配位的Zn 2+离子结合在蛋白质表面，不与Ca 2+竞争。EF-手环内结合的Mg 2+和Mn 2+的相对位置与Ca 2+的相对位置相似，然而环的第12位中的Glu侧链（其与Ca 2+的双齿相互作用对于结构域打开是关键的）不直接结合Mn 2+或Mg 2+，并且空配体位置被水分子占据。我们的结论是，这种关键的相互作用是通过EF-手-β-支架对配体施加的特定立体化学约束来阻止的。结构表明，Mg 2+有助于关闭钙调蛋白活性和可能的其他EF-手蛋白在静息水平的Ca 2+。Mg 2+结合的N-CaM结构也提供了一个独特的观点，瞬时结合水合金属离子，并建议在金属诱导的构象变化的水合水的作用。
Calmodulin (CaM), a member of the EF-hand superfamily, regulates many aspects of the cell function by responding specifically to micromolar concentrations of Ca2+ in the presence of ~1000× higher concentration of cellular Mg2+. To explain the structural basis of metal ion binding specificity we have solved the X-ray structures of the N-terminal domain of calmodulin (N-CaM) in complexes with Mg2+, Mn2+ and Zn2+. In contrast to Ca2+, which induces domain opening in CaM, octahedrally coordinated Mg2+ and Mn2+ stabilize the closed-domain, apo-like conformation, while tetrahedrally coordinated Zn2+ ions bind at the protein surface and do not compete with Ca2+. The relative positions of bound Mg2+ and Mn2+ within the EF-hand loops are similar to those of Ca2+, however the Glu sidechain in the 12th position of the loop, whose bidentate interaction with Ca2+ is critical for domain opening, does not bind directly to either Mn2+ or Mg2+ and the vacant ligand position is occupied by a water molecule. We conclude that this critical interaction is prevented by specific stereochemical constraints imposed on the ligands by the EF-hand-β-scaffold. The structures suggest that Mg2+ contributes to the switching off of calmodulin activity and possibly other EF-hand proteins at the resting levels of Ca2+. The Mg2+-bound N-CaM structure also provides a unique view of a transiently bound hydrated metal ion and suggests a role for the hydration water in the metal induced conformational change.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1002/prot.340210307
发表时间：
1995-03-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
DEERFIELD, DW;FOX, DJ;PEDERSEN, LG
通讯作者：
PEDERSEN, LG
影响因子：
5.7
作者：
Evenäs, J;Malmendal, A;Akke, M
通讯作者：
Akke, M
DOI：
10.1107/s0907444902016657
发表时间：
2002-11-01
影响因子：
2.2
作者：
Adams, PD;Grosse-Kunstleve, RW;Terwilliger, TC
通讯作者：
Terwilliger, TC
影响因子：
8
作者：
Andersson, M;Malmendal, A;Svensson, LA
通讯作者：
Svensson, LA