Acidic/IQ motif regulator of calmodulin
Acidic/IQ motif regulator of calmodulin
复制标题
DOI：
10.1074/jbc.m703831200
复制
发表时间：
2008-01-18
影响因子：
4.8
通讯作者：
Kleerekoper, Quinn K.
中科院分区：
文献类型：
--
作者：
Putkey, John A.;Waxham, M. Neal;Kleerekoper, Quinn K.
小IQ基序蛋白PEP-19（62个氨基酸）和RC3（78个氨基酸）极大地加快了钙调蛋白c结构域III和IV位点的Ca2+结合速率。我们在这里表明，PEP-19降低了Ca2+结合到III和IV位点的协同度，我们提出了一个模型，表明这可以增加Ca2+结合速率常数。比较序列分析表明，PEP-19残基28 ~ 58在其他蛋白中具有保守性。该区域包括IQ基序（氨基酸39-62）和邻近的酸性氨基酸簇（氨基酸28-40）。合成肽跨越残基28-62忠实地模仿完整的PEP-19，增加Ca2+结合和解离的速率，以及优先结合到CaM的c结构域。相反，仅编码核心IQ基序的肽不调节Ca2+结合，并结合到CaM上的多个位点。只包含酸性区域的肽不会与CaM结合。这些结果表明，PEP-19具有一个新的酸性/IQ CaM调控基序，其中IQ序列提供了一个靶向功能，允许PEP-19与CaM结合，而酸性残基修饰了这种相互作用的性质，并且对于调节Ca2+结合到CaM的c结构域是必不可少的。
The small IQ motif proteins PEP-19 (62 amino acids) and RC3 (78 amino acids) greatly accelerate the rates of Ca2+ binding to sites III and IV in the C-domain of calmodulin (CaM). We show here that PEP-19 decreases the degree of cooperativity of Ca2+ binding to sites III and IV, and we present a model showing that this could increase Ca2+ binding rate constants. Comparative sequence analysis showed that residues 28 to 58 from PEP-19 are conserved in other proteins. This region includes the IQ motif (amino acids 39-62), and an adjacent acidic cluster of amino acids (amino acids 28-40). A synthetic peptide spanning residues 28-62 faithfully mimics intact PEP-19 with respect to increasing the rates of Ca2+ association and dissociation, as well as binding preferentially to the C-domain of CaM. In contrast, a peptide encoding only the core IQ motif does not modulate Ca2+ binding, and binds to multiple sites on CaM. A peptide that includes only the acidic region does not bind to CaM. These results show that PEP-19 has a novel acidic/IQ CaM regulatory motif in which the IQ sequence provides a targeting function that allows binding of PEP-19 to CaM, whereas the acidic residues modify the nature of this interaction, and are essential for modulating Ca2+ binding to the C-domain of CaM.