STRUCTURE OF A NOVEL INSP3 RECEPTOR
STRUCTURE OF A NOVEL INSP3 RECEPTOR
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DOI：
10.1002/j.1460-2075.1991.tb04882.x
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发表时间：
1991-11-01
期刊：
影响因子：
11.4
通讯作者：
MIGNERY, GA
中科院分区：
文献类型：
--
作者：
SUDHOF, TC;NEWTON, CL;MIGNERY, GA
肌醇 1,4,5-三磷酸 (InsP3) 构成主要的细胞内第二信使，可转导许多生长因子和神经递质信号。 InsP3 通过与与 Ca2+ 通道偶联的特定受体结合，导致细胞内储存的 Ca2+ 释放。来自小脑的一种此类受体先前已被广泛表征。我们现在已经确定了第二种新型 InsP3 受体的完整结构，我们将其称为 2 型 InsP3 受体，而不是小脑 1 型 InsP3 受体。 2 型 InsP3 受体与小脑 1 型 InsP3 受体具有相同的总体结构设计，两者具有 69% 的序列同一性。 2型受体氨基末端1078个氨基酸的表达表明InsP3与2型受体的高亲和力结合，具有与1型受体相似的特异性但更高的亲和力。这些结果表明大脑中存在多种类型的 InsP3 受体，并提出了细胞内 Ca2+ 信号传导可能涉及多种途径的可能性，这些途径具有依赖于不同 InsP3 受体的不同调节特性。
Inositol 1,4,5-trisphosphate (InsP3) constitutes a major intracellular second messenger that transduces many growth factor and neurotransmitter signals. InsP3 causes the release of Ca2+ from intracellular stores by binding to specific receptors that are coupled to Ca2+ channels. One such receptor from cerebellum has previously been extensively characterized. We have now determined the full structure of a second, novel InsP3 receptor which we refer to as type 2 InsP3 receptor as opposed to the cerebellar type 1 InsP3 receptor. The type 2 InsP3 receptor has the same general structural design as the cerebellar type 1 InsP3 receptor with which it shares 69% sequence identity. Expression of the amino-terminal 1078 amino acids of the type 2 receptor demonstrates high affinity binding of InsP3 to the type 2 receptor with a similar specificity but higher affinity than observed for the type 1 receptor. These results demonstrate the presence of several types of InsP3 receptor in brain and raise the possibility that intracellular Ca2+ signaling may involve multiple pathways with different regulatory properties dependent on different InsP3 receptors.