Journal Article

Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans

Draczkowski, Piotr, Khoo, Kay-Hooi, Chang, Yuan-Chih, Chang, Hui-Wen, Hsu, Shang-Te Danny, Wu, Kuen-Phon, Ko, Tzu-Ping, Yang, Tzu-Jing, Chang, Yen-Chen, Chien, Yu-Chun

2020

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Biochemistry / Biological Sciences / Coronaviridae / Coronavirus, Feline - chemistry / Coronaviruses / Cryoelectron Microscopy / Feline infectious peritonitis / Galectins - chemistry / Glycosylation / HEK293 Cells / Humans / Mannose / Mannose - chemistry / Mass spectrometry / Mass spectroscopy / N-glycans / Pathogenesis / Peritonitis / PNAS Plus / Polysaccharides / Protein Conformation / Protein structure / Proteins / Spike Glycoprotein, Coronavirus - chemistry / Spike protein / Viruses