Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor

Guiqing Peng, Dawei Sun, Kanagalaghatta R. Rajashankar, Zhaohui Qian, Kathryn V. Holmes, Fang Li

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same β-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusive protein-protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/ CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the β-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.

Original languageEnglish (US)
Pages (from-to)10696-10701
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number26
DOIs
StatePublished - Jun 28 2011

Keywords

  • Carcinoembryonic antigen-related cell adhesion molecule 1 binding by coronaviruses
  • Coronavirus evolution
  • Galectin-like N-terminal domain of coronavirus spike proteins
  • Sugar binding by coronaviruses

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