Walker D, Bichet D, Campbell K P, De Waard M
INSERM U464, Institut Fédératif Jean Roche, Faculté de Médecine Nord, Marseille, France.
J Biol Chem. 1998 Jan 23;273(4):2361-7. doi: 10.1074/jbc.273.4.2361.
The voltage-gated calcium channel beta subunit is a cytoplasmic protein that stimulates activity of the channel-forming subunit, alpha 1, in several ways. Complementary binding sites on alpha 1 and beta have been identified that are highly conserved among isoforms of the two subunits, but this interaction alone does not account for all of the functional effects of the beta subunit. We describe here the characterization in vitro of a second interaction, involving the carboxyl-terminal cytoplasmic domain of alpha 1A and showing specificity for the beta 4 (and to a lesser extent beta 2a) isoform. A deletion and chimera approach showed that the carboxyl-terminal region of beta 4, poorly conserved between beta isoforms, contains the interaction site and plays a role in the regulation of channel inactivation kinetics. This is the first demonstration of a molecular basis for the specificity of functional effects seen for different combinations of these two channel components.
电压门控钙通道β亚基是一种胞质蛋白，它通过多种方式刺激形成通道的α1亚基的活性。已确定α1和β上的互补结合位点在这两个亚基的同工型中高度保守，但仅这种相互作用并不能解释β亚基的所有功能效应。我们在此描述了第二种相互作用的体外特性，该相互作用涉及α1A的羧基末端胞质结构域，并且对β4（以及程度较轻的β2a）同工型具有特异性。缺失和嵌合体方法表明，β4的羧基末端区域在β同工型之间保守性较差，包含相互作用位点，并在通道失活动力学的调节中起作用。这首次证明了这两种通道成分不同组合所产生功能效应特异性的分子基础。
