Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor
Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor
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DOI：
10.1016/j.molcel.2004.11.047
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发表时间：
2005-01-21
期刊：
影响因子：
16
通讯作者：
Ikura, M
中科院分区：
文献类型：
--
作者：
Bosanac, I;Yamazaki, H;Ikura, M
肌醇1,4,5-三磷酸（IP3）与IP3受体氨基末端区域的结合促进Ca2+从内质网释放。在氨基端，直接位于IP3结合核心结构域前的前220个残基在IP3结合抑制和调节蛋白相互作用中起关键作用。在这里，我们展示了小鼠1型IP3受体在1.8埃时的抑制域的晶体结构。抑制区显示类似于锤子的形状，包含形成β -三叶折叠的Head子域和具有螺旋-转-螺旋结构的Arm子域。Head亚结构域上的保守区域似乎与IP3结合核心结构域相互作用，并且靠近先前提出的Homer、RACK1、calmodulin和CaBP1的结合位点。目前的研究揭示了受体对配体的敏感性及其与细胞信号蛋白的通讯机制。
Binding of inositol 1,4,5-trisphosphate (IP3) to the amino-terminal region Of IP3 receptor promotes Ca2+ release from the endoplasmic reticulum. Within the amino terminus, the first 220 residues directly preceding the IP3 binding core domain play a key role in IP3 binding suppression and regulatory protein interaction. Here we present a crystal structure of the suppressor domain of the mouse type 1 IP3 receptor at 1.8 Angstrom. Displaying a shape akin to a hammer, the suppressor region contains a Head subdomain forming the beta-trefoil fold and an Arm subdomain possessing a helix-turn-helix structure. The conserved region on the Head subdomain appeared to interact with the IP3 binding core domain and is in close proximity to the previously proposed binding sites of Homer, RACK1, calmodulin, and CaBP1. The present study sheds light onto the mechanism underlying the receptor's sensitivity to the ligand and its communication with cellular signaling proteins.