THE AMINO-TERMINUS OF A CALCIUM-CHANNEL BETA-SUBUNIT SETS RATES OF CHANNEL INACTIVATION INDEPENDENTLY OF THE SUBUNITS EFFECT ON ACTIVATION
THE AMINO-TERMINUS OF A CALCIUM-CHANNEL BETA-SUBUNIT SETS RATES OF CHANNEL INACTIVATION INDEPENDENTLY OF THE SUBUNITS EFFECT ON ACTIVATION
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DOI：
10.1016/0896-6273(94)90428-6
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发表时间：
1994-12-01
期刊：
影响因子：
16.2
通讯作者：
BIRNBAUMER, L
中科院分区：
文献类型：
--
作者：
OLCESE, R;QIN, N;BIRNBAUMER, L
电压门控钙通道的α(1)和β亚基均存在分子多样性。C型α(1)(α(1C))的电压传感和孔道开放之间的耦合被2型β亚基(β(2))改善，而E-型α(1)β复合体的失活速度取决于β的性质。我们比较了1型和2型β亚基对人类E型α(1)(α(1E))激活的影响，以及它们对灭活的影响，就像在非洲爪哇卵母细胞中看到的那样。β亚型以相似的方式刺激激活，但对失活的影响不同，甚至是相反的方向。β亚基有一个共同的中心核心，但其N-末端和C-末端以及中央区域不同。对失活有相反作用的β(1)和β(2)亚基之间的N-末端嵌合体导致了它们的作用的相互转移。我们的结论是，β对α(1)的激活和失活的调节是可分离的事件，并且β的N末端是决定铝失活的速率和电压的重要结构决定因素之一。
There is molecular diversity in both alpha(1) and beta subunits of voltage-gated Ca2+ channels. Coupling between voltage sensing and pore opening of the C-type alpha(1) (alpha(1C)) is improved by the type 2 beta subunit (beta(2)), and E-type alpha(1) beta complexes inactivate at different rates depending on the nature of beta. We compared the effects of type 1 and 2 beta subunits on activation of the human E-type alpha(1) (alpha(1E)) with the effects they have on inactivation, as seen in Xenopus oocytes. The beta subtypes stimulated activation in similar fashion but affected inactivation differently, and even in opposing directions. beta subunits have a common central core but differ in their N- and C-termini and in a central region. N-terminal chimeras between beta(1) and beta(2) subunits that have opposing effects on inactivation resulted in the reciprocal transfer of their effects. We conclude that regulation of activation and inactivation of alpha(1) by beta are separable events and that the N-terminus of beta is one of the structural determinants important in setting the rate and voltage at which an al inactivates.