Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry

Jian Shang, Yushun Wan, Chang Liu, Boyd Yount, Kendra Gully, Yang Yang, Ashley Auerbach, Guiqing Peng, Ralph Baric, Fang Li

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Coronaviruses recognize a variety of receptors using different domains of their envelope-anchored spike protein. How these diverse receptor recognition patterns affect viral entry is unknown. Mouse hepatitis coronavirus (MHV) is the only known coronavirus that uses the N-terminal domain (NTD) of its spike to recognize a protein receptor, CEACAM1a. Here we determined the cryo-EM structure of MHV spike complexed with mouse CEACAM1a. The trimeric spike contains three receptor-binding S1 heads sitting on top of a trimeric membrane-fusion S2 stalk. Three receptor molecules bind to the sides of the spike trimer, where three NTDs are located. Receptor binding induces structural changes in the spike, weakening the interactions between S1 and S2. Using protease sensitivity and negative-stain EM analyses, we further showed that after protease treatment of the spike, receptor binding facilitated the dissociation of S1 from S2, allowing S2 to transition from pre-fusion to post-fusion conformation. Together these results reveal a new role of receptor binding in MHV entry: in addition to its well-characterized role in viral attachment to host cells, receptor binding also induces the conformational change of the spike and hence the fusion of viral and host membranes. Our study provides new mechanistic insight into coronavirus entry and highlights the diverse entry mechanisms used by different viruses.

Original languageEnglish (US)
Article numbere1008392
JournalPLoS pathogens
Issue number3
StatePublished - Mar 9 2020

Bibliographical note

Funding Information:
Funding: This work was supported by R01AI089728 (to F. Li) from National Institute of Allergy and Infectious Diseases (https://www.niaid. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
Copyright: © 2020 Shang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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