近日，上海科技大学大学杨海涛、饶子和、复旦大学孙磊研究组揭示了TMPRSS2和聚糖受体协同促进冠状病毒进入。相关论文于2024年7月3日发表在《细胞》杂志上。
小组研究了HCoV-HKU1C刺突在无活性状态、聚糖激活状态和功能锚定状态下的情况，发现唾液聚糖结合诱导了NTD的构象变化，并促进刺突邻近的RBD打开以供TMPRSS2识别，显示了HCoV-HKU1进入的协同机制。HCoV-HKU1的RBD具有一个插入亚结构，该插入亚结构通过三个以前未发现的界面识别TMPRSS2。此外，HCoV-HKU1A的结构研究结合诱变和结合分析证实了HCoV-HKU1采用保守的受体识别模式。
这些研究促进了他们对进入过程中复杂的病毒-宿主相互作用的理解，为开发针对冠状病毒相关疾病的新疗法奠定了基础。
据了解，冠状病毒的进入是由宿主细胞受体的刺突识别启动的，涉及蛋白质和/或聚糖受体。最近，TMPRSS2与唾液聚糖一起被鉴定为HCoV-HKU1的蛋白乙酰化受体。然而，病毒进入的潜在机制仍然未知。
附：英文原文
Title: TMPRSS2 and glycan receptors synergistically facilitate coronavirus entry
Author: Haofeng Wang, Xiaoce Liu, Xiang Zhang, Zhuoqian Zhao, Yuchi Lu, Dingzhe Pu, Zeyang Zhang, Jie Chen, Yajie Wang, Mengfei Li, Xuxue Dong, Yinkai Duan, Yujia He, Qiyu Mao, Hangtian Guo, Haoran Sun, Yihan Zhou, Qi Yang, Yan Gao, Xiuna Yang, Hongzhi Cao, Luke Guddat, Lei Sun, Zihe Rao, Haitao Yang
Issue&Volume: 2024-07-03
Abstract: The entry of coronaviruses is initiated by spike recognition of host cellular receptors,involving proteinaceous and/or glycan receptors. Recently, TMPRSS2 was identifiedas the proteinaceous receptor for HCoV-HKU1 alongside sialoglycan as a glycan receptor.However, the underlying mechanisms for viral entry remain unknown. Here, we investigatedthe HCoV-HKU1C spike in the inactive, glycan-activated, and functionally anchoredstates, revealing that sialoglycan binding induces a conformational change of theNTD and promotes the neighboring RBD of the spike to open for TMPRSS2 recognition,exhibiting a synergistic mechanism for the entry of HCoV-HKU1. The RBD of HCoV-HKU1features an insertion subdomain that recognizes TMPRSS2 through three previously undiscoveredinterfaces. Furthermore, structural investigation of HCoV-HKU1A in combination withmutagenesis and binding assays confirms a conserved receptor recognition pattern adoptedby HCoV-HKU1. These studies advance our understanding of the complex viral-host interactionsduring entry, laying the groundwork for developing new therapeutics against coronavirus-associateddiseases.
DOI: 10.1016/j.cell.2024.06.016
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00656-1