The Endoplasmic Reticulum Chaperone Cosmc Directly Promotes in Vitro Folding of T-synthase
The Endoplasmic Reticulum Chaperone Cosmc Directly Promotes in Vitro Folding of T-synthase
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DOI：
10.1074/jbc.m109.065169
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发表时间：
2010-01-22
影响因子：
4.8
通讯作者：
Cummings, Richard D.
中科院分区：
文献类型：
--
作者：
Aryal, Rajindra P.;Ju, Tongzhong;Cummings, Richard D.
T-合酶是动物细胞糖蛋白中核心10-聚糖（Gal β 1-3GalNAc α 1-Ser/Thr）生物合成所必需的关键β 3-半乳糖基转移酶。在这里，我们描述了一种新的内质网定位的分子伴侣称为Cosmc的特异性相互作用与部分变性的T-合成酶在体外引起部分恢复活动的能力。相比之下，在Tn综合征患者中观察到的Cosmc突变形式具有降低的伴侣功能。Cosmc的伴侣活性是特异性的，在体外不需要ATP，并且对T-合酶有效，但对另一种β-半乳糖基转移酶无效。Cosmc代表了第一个被鉴定为糖基转移酶折叠所需的ER分子伴侣。
The T-synthase is the key beta 3-galactosyltransferase essential for biosynthesis of core 1 O-glycans (Gal beta 1-3GalNAc alpha 1-Ser/Thr) in animal cell glycoproteins. Here we describe the novel ability of an endoplasmic reticulum-localized molecular chaperone termed Cosmc to specifically interact with partly denatured T-synthase in vitro to cause partial restoration of activity. By contrast, a mutated form of Cosmc observed in patients with Tn syndrome has reduced chaperone function. The chaperone activity of Cosmc is specific, does not require ATP in vitro, and is effective toward T-synthase but not another beta-galactosyltransferase. Cosmc represents the first ER chaperone identified to be required for folding of a glycosyltransferase.