Cis-prenyltransferase (cis-PTase) catalyzes the rate-limiting step in the synthesis of glycosyl carrier lipids required for protein glycosylation in the lumen of endoplasmic reticulum. Here we report the crystal structure of the human NgBR/DHDDS complex, which represents the first atomic resolution structure for any heterodimeric cis-PTase. The crystal structure sheds light on how NgBR stabilizes DHDDS through dimerization, participates in the enzymes active site through its C-terminal -RXG- motif, and how phospholipids markedly stimulate cis-PTase activity.Comparison of NgBR/DHDDS with homodimeric cis-PTase structures leads to a model where the elongating isoprene chain extends beyond the enzymes active site tunnel, and an insert within the alpha 3 helix helps to stabilize this energetically unfavorable state to enable long chain synthesis to occur. These data provide unique insights into how heterodimeric cis-PTases have evolved from their ancestral, homodimeric forms to fulfill their function in long chain polyprenol synthesis.

中文翻译：

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异二聚体顺式异戊二烯基转移酶NgBR / DHDDS复合物的结构阐明揭示了调节蛋白质糖基化的新见解。

顺式异戊二烯基转移酶（cis-PTase）催化内质网腔蛋白糖基化所需的糖基载体脂质合成中的限速步骤。在这里，我们报告人类NgBR / DHDDS复合物的晶体结构，它代表任何异二聚体顺式PTase的第一个原子拆分结构。晶体结构揭示了NgBR如何通过二聚作用稳定DHDDS，如何通过其C端-RXG-图案参与酶的活性位点以及磷脂如何显着刺激顺式PTase活性.NgBR / DHDDS与同型二聚体顺式PTase结构的比较。导致模型，其中异戊二烯的延伸链延伸超出了酶的活性位点隧道，α3螺旋内的插入片段有助于稳定这种在能量上不利的状态，从而可以进行长链合成。这些数据提供了关于异二聚体顺式PTases如何从其祖先的同二聚体形式进化而实现其在长链聚戊二烯合成中的功能的独特见解。