Cryo-electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B
Cryo-electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B
复制标题
DOI：
10.1126/science.aaz3505
复制
发表时间：
2019-12-13
期刊：
影响因子：
56.9
通讯作者：
Locher, Kaspar P.
中科院分区：
文献类型：
--
作者：
Ramirez, Ana S.;Kowal, Julia;Locher, Kaspar P.
寡糖基转移酶（OST）催化高甘露糖聚糖转移到内质网中的分泌蛋白上。哺乳动物表达两种不同的OST复合物，以共翻译（OST-A）或易位后（OST-B）方式起作用。在这里，我们提出了高分辨率的冷冻电子显微镜结构的人OST-A和OST-B。虽然它们具有相似的整体结构，但催化亚基STT 3A和STT 3B的结构差异促进了与不同OST亚基的接触，OST-A中的DC 2和OST-B中的MAGT 1。在OST-A中，与TMEM 258和STT 3A的相互作用允许核糖体蛋白-I形成可以结合到翻译核糖体的四螺旋束，而在OST-B中等同区域是无序的。我们观察到一个受体肽和dolichylphosphate结合到STT 3B，但只有dolichylphosphate在STT 3A，表明不同的亲和力的两个OST复合物的蛋白质底物。
Oligosaccharyltransferase (OST) catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum. Mammals express two distinct OST complexes that act in a cotranslational (OST-A) or posttranslocational (OST-B) manner. Here, we present high-resolution cryo-electron microscopy structures of human OST-A and OST-B. Although they have similar overall architectures, structural differences in the catalytic subunits STT3A and STT3B facilitate contacts to distinct OST subunits, DC2 in OST-A and MAGT1 in OST-B. In OST-A, interactions with TMEM258 and STT3A allow ribophorin-I to form a four-helix bundle that can bind to a translating ribosome, whereas the equivalent region is disordered in OST-B. We observed an acceptor peptide and dolichylphosphate bound to STT3B, but only dolichylphosphate in STT3A, suggesting distinct affinities of the two OST complexes for protein substrates.