人冠状病毒229E宿主识别的分子基础。

Molecular basis of host recognition of human coronavirus 229E.

作者信息

Tsai Yu-Xi, Chien Yu-Chun, Hsu Min-Feng, Khoo Kay-Hooi, Hsu Shang-Te Danny

机构信息

Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.

Institute of Biochemical Sciences, National Taiwan University, Taipei, 10617, Taiwan.

出版信息

Nat Commun. 2025 Feb 27;16(1):2045. doi: 10.1038/s41467-025-57359-8.

DOI:10.1038/s41467-025-57359-8

PMID:40016196

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11868633/

Abstract

Human coronavirus 229E (HCoV-229E) is the earliest CoV found to infect humans. It binds to the human aminopeptidase N (hAPN) through the receptor binding domain (RBD) of its spike (S) protein to achieve host recognition. We present the cryo-electron microscopy structure of two HCoV-229E S protein in complex with a dimeric hAPN to provide structural insights on how the HCoV-229E S protein opens up its RBD to engage with its host receptor, information that is currently missing among alphacoronaviruses to which HCoV-229E belong. We quantitatively profile the glycosylation of HCoV-229E S protein and hAPN to deduce the glyco-shielding effects pertinent to antigenicity and host recognition. Finally, we present an atomic model of fully glycosylated HCoV-229E S in complex with hAPN anchored on their respective membrane bilayers to recapitulate the structural basis of the first step of host infection by HCoV-229E.

摘要

人冠状病毒229E（HCoV - 229E）是最早发现可感染人类的冠状病毒。它通过其刺突（S）蛋白的受体结合结构域（RBD）与人氨肽酶N（hAPN）结合，以实现对宿主的识别。我们展示了两种HCoV - 229E S蛋白与二聚体hAPN复合物的冷冻电镜结构，以提供关于HCoV - 229E S蛋白如何打开其RBD与宿主受体结合的结构见解，而这一信息在HCoV - 229E所属的α冠状病毒中目前尚缺。我们定量分析了HCoV - 229E S蛋白和hAPN的糖基化情况，以推断与抗原性和宿主识别相关的糖屏蔽效应。最后，我们展示了完全糖基化的HCoV - 229E S与锚定在各自膜双层上的hAPN复合物的原子模型，以概括HCoV - 229E宿主感染第一步的结构基础。