Essential CaVβ modulatory properties are AID-independent
Essential CaVβ modulatory properties are AID-independent
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DOI：
10.1038/nsmb909
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发表时间：
2005-04-01
影响因子：
16.8
通讯作者：
Pitt, GS
中科院分区：
文献类型：
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作者：
Maltez, JM;Nunziato, DA;Pitt, GS
电压门控 Ca2+ 通道 β (Ca-v β) 亚基具有高度保守的核心，由相互作用的 Src 同源 3 和鸟苷酸激酶结构域组成，并推测通过 AID（成孔 α(1) 亚基中的主要相互作用位点）发挥其作用。这种刻板的相互作用并不能解释单个 Ca-v β 亚基如何差异调节 α(1) 亚基。在这里，我们证明 AID 对于关键的 Ca-v beta 调节特性既不是必要的也不是充分的。完整的调制取决于 AID 之外的附加接触，并且在最近的晶体结构中未显示。这些数据为理解 Ca-v β 调节提供了新的背景，表明 AID 相互作用定向 Ca-v β 核心，从而允许额外的同种型特异性 Ca-v α(1)-Ca-v β 相互作用，这些相互作用是每个 Ca-v α(1)-Ca-v β 对的特定调节的基础，而不是作为调节的主要位点。
Voltage-gated Ca2+ channel beta (Ca-v beta) subunits have a highly conserved core consisting of interacting Src homology 3 and guanylate kinase domains, and are postulated to exert their effects through AID, the major interaction site in the pore-forming alpha(1) subunit. This stereotypical interaction does not explain how individual Ca-v beta subunits modulate alpha(1) subunits differentially. Here we show that AID is neither necessary nor sufficient for critical Ca-v beta regulatory properties. Complete modulation depends on additional contacts that are exclusive of AID and not revealed in recent crystal structures. These data offer a new context for understanding Ca-v beta modulation, suggesting that the AID interaction orients the Ca-v beta core so as to permit additional isoform-specific Ca-v alpha(1)-Ca-v beta interactions that underlie the particular regulation seen with each Ca-v alpha(1)-Ca-v beta pair, rather than as the main site of regulation.