title: Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor.
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.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Guiqing
authors.initials: G
authors.lastname: Peng
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.forename: Kanagalaghatta R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Qian
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Holmes
authors.forename: Fang
authors.initials: F
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D000085064:Receptors, Coronavirus; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D000085064:Receptors, Coronavirus; D011991:Receptors, Virus