Subject(s)
ABO Blood-Group System/genetics , Alveolar Epithelial Cells/metabolism , Oligosaccharides/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Sequence , COVID-19 , Carbohydrate Conformation , Carbohydrate Sequence , Consensus Sequence , Erythrocyte Membrane/metabolism , Galectin 4/chemistry , Galectins/chemistry , Genetic Predisposition to Disease , Humans , Oligosaccharides/genetics , Oligosaccharides, Branched-Chain , Organ Specificity , Protein Binding , Protein Domains , SARS-CoV-2 , Sequence Alignment , Sequence Homology, Amino Acid , Spike Glycoprotein, Coronavirus/chemistry , Substrate SpecificityABSTRACT
Feline infectious peritonitis virus (FIPV) is an alphacoronavirus that causes a nearly 100% mortality rate without effective treatment. Here we report a 3.3-Å cryoelectron microscopy (cryo-EM) structure of the serotype I FIPV spike (S) protein, which is responsible for host recognition and viral entry. Mass spectrometry provided site-specific compositions of densely distributed high-mannose and complex-type N-glycans that account for 1/4 of the total molecular mass; most of the N-glycans could be visualized by cryo-EM. Specifically, the N-glycans that wedge between 2 galectin-like domains within the S1 subunit of FIPV S protein result in a unique propeller-like conformation, underscoring the importance of glycosylation in maintaining protein structures. The cleavage site within the S2 subunit responsible for activation also showed distinct structural features and glycosylation. These structural insights provide a blueprint for a better molecular understanding of the pathogenesis of FIP.