An essential dimer-forming subregion of the endoplasmic reticulum stress sensor Ire1
An essential dimer-forming subregion of the endoplasmic reticulum stress sensor Ire1
复制标题
DOI：
10.1042/bj20050640
复制
发表时间：
2005-10-01
影响因子：
4.1
通讯作者：
Kohno, K
中科院分区：
文献类型：
--
作者：
Oikawa, D;Kumata, Y;Kohno, K
I型跨膜蛋白Ire1的腔结构域通过一种未明确的机制感知内质网应激，从而上调未折叠蛋白反应的信号通路。此前，我们提出酵母Ire1的腔结构域从N端开始依次被划分为五个亚区，称为亚区I - V。当亚区II或IV发生内部缺失时，Ire1失去活性。在本文中，我们表明由Ire1腔结构域组成的重组蛋白的部分蛋白水解作用提示亚区II - IV紧密折叠。我们还表明亚区II - IV的重组蛋白形成同源二聚体，并且亚区IV的内部缺失会损害这种同源二聚体的形成。此外，亚区IV的重组片段表现出自我结合能力。因此，尽管其序列在进化上保守性较低，但亚区IV在促进Ire1二聚体形成中起着至关重要的作用。
The luminal domain of the type I transmembrane protein Ire1 senses endoplasmic reticulum stress by an undefined mechanism to up-regulate the signalling pathway for the unfolded protein response. Previously, we proposed that the luminal domain of yeast Ire1 is divided into five subregions, termed subregions I-V sequentially from the N-terminus. Ire1 lost activity when internal deletions of subregion II or IV were made. In the present paper, we show that partial proteolysis of a recombinant protein consisting of the Ire1 luminal domain suggests that subregions II-IV are tightly folded. We also show that a recombinant protein of subregions II-IV formed homodimers, and that this homodimer formation was impaired by an internal deletion of subregion IV. Furthermore, recombinant fragments of subregion IV exhibited a self-binding ability. Therefore, although its sequence is little conserved evolutionarily, subregion IV plays an essential role to promote Ire1 dimer formation.