The L-type Ca2+ channel CaV 1.2 governs gene expression, cardiac contraction, and neuronal activity. Binding of α-actinin to the IQ motif of CaV 1.2 supports its surface localization and postsynaptic targeting in neurons. We report a bi-functional mechanism that restricts CaV 1.2 activity to its target sites. We solved separate NMR structures of the IQ motif (residues 1,646-1,664) bound to α-actinin-1 and to apo-calmodulin (apoCaM). The CaV 1.2 K1647A and Y1649A mutations, which impair α-actinin-1 but not apoCaM binding, but not the F1658A and K1662E mutations, which impair apoCaM but not α-actinin-1 binding, decreased single-channel open probability, gating charge movement, and its coupling to channel opening. Thus, α-actinin recruits CaV 1.2 to defined surface regions and simultaneously boosts its open probability so that CaV 1.2 is mostly active when appropriately localized.

中文翻译：

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α-Actinin-1促进L型Ca2 +通道Cav 1.2的活性。

L型Ca2 +通道CaV 1.2控制基因表达，心脏收缩和神经元活动。α-辅肌动蛋白与CaV 1.2的IQ基序的结合支持其表面定位和神经元中的突触后靶向。我们报告了一种双功能机制，将CaV 1.2活性限制在其目标位点。我们解决了结合到α-actinin-1和apo-钙调蛋白（apoCaM）的IQ基序（残基1,646-1,664）的单独NMR结构。CaV 1.2 K1647A和Y1649A突变会损害α-actinin-1但不会破坏apoCaM结合，但不会破坏F1658A和K1662E突变会损害apoCaM但不会破坏α-actinin-1结合，从而降低单通道打开概率，门控电荷移动，并将其耦合到通道开口。因此，α-肌动蛋白将CaV 1.2募集到定义的表面区域，同时提高其开放概率，从而使CaV 1。