ERp27, a new non-catalytic endoplasmic reticulum-located human protein disulfide isomerase family member, interacts with ERp57
ERp27, a new non-catalytic endoplasmic reticulum-located human protein disulfide isomerase family member, interacts with ERp57
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DOI：
10.1074/jbc.m604314200
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发表时间：
2006-11-03
影响因子：
4.8
通讯作者：
Ruddock, Lloyd W.
中科院分区：
文献类型：
--
作者：
Alanen, Heli I.;Williamson, Richard A.;Ruddock, Lloyd W.
内质网中的蛋白质折叠和质量控制是我们目前的理解还远未完成的关键过程。在这里，我们描述了一种新的人类 27.7-kDa 蛋白 (ERp27) 的功能特征。我们发现 ERp27 是一种位于内质网的双结构域蛋白，与蛋白质二硫键异构酶的非催化 b 和 b' 结构域同源。 ERp27 被证明可以结合 Delta-so-matostatin（蛋白质二硫键异构酶底物结合的标准测试肽），并且这种能力位于 ERp27 的第二个结构域。人 ERp27 和人蛋白质二硫键异构酶的比对允许推定鉴定 ERp27 的肽结合位点，表明蛋白质二硫键异构酶家族内主要底物结合位点位置的保守性。 NMR 研究揭示了 ERp27 的 b' 样结构域在底物结合时发生显着的构象变化，该变化不仅仅局限于底物结合位点。此外，我们报道ERp27在体外和体内均通过ERp57结合钙网蛋白的类似机制与ERp57结合。
Protein folding and quality control in the endoplasmic reticulum are critical processes for which our current understanding is far from complete. Here we describe the functional characterization of a new human 27.7-kDa protein (ERp27). We show that ERp27 is a two-domain protein located in the endoplasmic reticulum that is homologous to the non-catalytic b and b' domains of protein disulfide isomerase. ERp27 was shown to bind Delta-so-matostatin, the standard test peptide for protein disulfide isomerase-substrate binding, and this ability was localized to the second domain of ERp27. An alignment of human ERp27 and human protein disulfide isomerase allowed for the putative identification of the peptide binding site of ERp27 indicating conservation of the location of the primary substrate binding site within the protein disulfide isomerase family. NMR studies revealed a significant conformational change in the b'-like domain of ERp27 upon substrate binding, which was not just localized to the substrate binding site. In addition, we report that ERp27 is bound by ERp57 both in vitro and in vivo by a similar mechanism by which ERp57 binds calreticulin.