Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Cav1.2 calcium channel
Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Cav1.2 calcium channel
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DOI：
10.1016/j.str.2005.09.021
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发表时间：
2005-12-01
期刊：
影响因子：
5.7
通讯作者：
Quiocho, FA
中科院分区：
文献类型：
--
作者：
Fallon, JL;Halling, DB;Quiocho, FA
钙通道的钙依赖失活(CDI)和易化(CDF)需要钙调蛋白与成孔亚基羧基末端的IQ基序结合。我们给出了与Ca(V)1.2的IQ结构域相对应的21个残基上结合的钙-钙调蛋白的1.45埃晶体结构。这种结构表明钙调蛋白与IQ结构域的平行结合是由疏水相互作用控制的。多肽中I1672和Q1673残基突变为丙氨酸，这会消除通道中的CDI，但不会显著改变CDF的结构。钙饱和CaM的两个叶都与IQ肽结合，但异亮氨酸1672被掩埋，异亮氨酸1672被认为形成了驱动CDI的分子内相互作用。这些发现表明，这种结构可能代表了CDF中钙调蛋白的构象。
Ca2+-dependent inactivation (CDI) and facilitation (CDF) of the Ca(v)1.2 Ca2+ channel require calmodulin binding to a putative IQ motif in the carboxy-terminal tail of the pore-forming subunit. We present the 1.45 angstrom crystal structure of Ca2+-calmodulin bound to a 21 residue peptide corresponding to the IQ domain of Ca(v)1.2. This structure shows that parallel binding of calmodulin to the IQ domain is governed by hydrophobic interactions. Mutations of residues I1672 and Q1673 in the peptide to alanines, which abolish CDI but not CDF in the channel, do not greatly alter the structure. Both lobes of Ca2+-saturated CaM bind to the IQ peptide but isoleucine 1672, thought to form an intramolecular interaction that drives CDI, is buried. These findings suggest that this structure could represent the conformation that calmodulin assumes in CDF.