Huang Jiazhao, Yin Han, Yin Peiqi, Jian Xia, Song Siqi, Luan Junwen, Zhang Leiliang
Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Microbiol. 2019 Sep 6;10:2043. doi: 10.3389/fmicb.2019.02043. eCollection 2019.
Hepatitis C virus (HCV) entry is mediated by multiple co-receptors including scavenger receptor class B, type I (SR-BI). To elucidate the interactome of human SR-BI, we performed immunoprecipitation (IP) experiment coupled with mass spectrometry (MS) analysis. UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), a key component of calnexin cycle involved in protein glycosylation, was identified as a SR-BI-interacting protein. Silencing UGGT1 or N-glycosylation inhibitor treatment reduced SR-BI protein level. Further study demonstrated that human SR-BI was N-glycosylated at nine asparagines. Moreover, HCV entry and infection were reduced by the absence of UGGT1. Interestingly, silencing SR-BI reduced protein stability of UGGT1 and protein quality control function mediated by UGGT1. Our finding not only identified UGGT1 as a HCV host factor, but also identified a UGGT1-mediated protein folding function for SR-BI.
丙型肝炎病毒（HCV）的进入由多种共受体介导，包括B类清道夫受体I型（SR-BI）。为了阐明人类SR-BI的相互作用组，我们进行了免疫沉淀（IP）实验并结合质谱（MS）分析。UDP-葡萄糖：糖蛋白葡糖基转移酶1（UGGT1）是参与蛋白质糖基化的钙连蛋白循环的关键成分，被鉴定为与SR-BI相互作用的蛋白。沉默UGGT1或进行N-糖基化抑制剂处理可降低SR-BI蛋白水平。进一步研究表明，人类SR-BI在9个天冬酰胺处发生N-糖基化。此外，UGGT1缺失会降低HCV的进入和感染。有趣的是，沉默SR-BI会降低UGGT1的蛋白质稳定性以及UGGT1介导的蛋白质质量控制功能。我们的发现不仅将UGGT1鉴定为HCV宿主因子，还确定了UGGT1介导的SR-BI蛋白质折叠功能。
