In vivo interaction between the human dehydrodolichyl diphosphate synthase and the Niemann-Pick C2 protein revealed by a yeast two-hybrid system
In vivo interaction between the human dehydrodolichyl diphosphate synthase and the Niemann-Pick C2 protein revealed by a yeast two-hybrid system
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DOI：
10.1016/j.bbrc.2004.04.007
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发表时间：
2004-05-21
影响因子：
3.1
通讯作者：
Koyama, T
中科院分区：
文献类型：
--
作者：
Kharel, Y;Takahashi, S;Koyama, T
二磷酸脱氢多萜醇（Dehydrodolichyl diphosphate，DedolPP）合成酶催化异戊烯基二磷酸与法呢基二磷酸缩合生成DedolPP，DedolPP是多萜醇的生物合成前体，在真核细胞糖蛋白的生物合成中起着重要的糖载体作用。在某些病理过程中，如阿尔茨海默病或一些神经系统疾病，多萜醇已被证明在人脑中积累。为了理解真核生物中长胆醇的调节机制，我们使用全长人DedolPP合酶基因[Endo等人，BBA 1625（2003）291]作为诱饵进行酵母双杂交筛选，以发现一些与酶特异性相互作用的蛋白质。我们鉴定了尼曼-匹克C2型蛋白（NPC 2），以显示与人DedolPP合酶的特异性相互作用。通过体外免疫共沉淀实验进一步证实了这种相互作用，表明NPC 2和DedolPP合酶蛋白之间可能存在生理相互作用。(C)2004年爱思唯尔公司All rights reserved.
Dehydrodolichyl diphosphate (DedolPP) synthase catalyzes the sequential condensation of isopentenyl diphosphate with farnesyl diphosphate to synthesize DedolPP, a biosynthetic precursor for dolichol which plays an important role as a sugar-carrier lipid in the biosynthesis of glycoprotein in eukaryotic cells. During certain pathological processes like Alzheimer's disease or some neurological disorders, dolichol has been shown to accumulate in human brain. In order to understand the regulatory mechanism of dolichol in eukaryotes, we performed a yeast two-hybrid screen using full length human DedolPP synthase gene [Endo et al. BBA 1625 (2003) 291] as a bait to find some proteins specifically interacting with the enzyme. We identified Niemann-Pick Type C2 protein (NPC2) to show a specific interaction with human DedolPP synthase. This interaction was further confirmed by in vitro co-immunoprecipitation experiment, indicating the possible physiological interaction between NPC2 and DedolPP synthase proteins in human. (C) 2004 Elsevier Inc. All rights reserved.