In situ structure and dynamics of an alphacoronavirus spike protein by cryo-ET and cryo-EM.

Autor: Huang CY; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan., Draczkowski P; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Faculty of Pharmacy, Medical University of Lublin, ul. W. Chodzki 4a, 20-093, Lublin, Poland., Wang YS; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Institute of Biochemical Sciences, National Taiwan University, Taipei, 11529, Taiwan., Chang CY; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan., Chien YC; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Institute of Biochemical Sciences, National Taiwan University, Taipei, 11529, Taiwan., Cheng YH; Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan., Wu YM; Academia Sinica Cryo-EM Center, Academia Sinica, Taipei, 11529, Taiwan., Wang CH; Academia Sinica Cryo-EM Center, Academia Sinica, Taipei, 11529, Taiwan., Chang YC; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Academia Sinica Cryo-EM Center, Academia Sinica, Taipei, 11529, Taiwan., Chang YC; Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan., Yang TJ; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Institute of Biochemical Sciences, National Taiwan University, Taipei, 11529, Taiwan., Tsai YX; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Institute of Biochemical Sciences, National Taiwan University, Taipei, 11529, Taiwan., Khoo KH; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.; Institute of Biochemical Sciences, National Taiwan University, Taipei, 11529, Taiwan., Chang HW; Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan., Hsu SD; Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan. sthsu@gate.sinica.edu.tw.; Institute of Biochemical Sciences, National Taiwan University, Taipei, 11529, Taiwan. sthsu@gate.sinica.edu.tw.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Aug 19; Vol. 13 (1), pp. 4877. Date of Electronic Publication: 2022 Aug 19.
DOI: 10.1038/s41467-022-32588-3
Abstrakt: Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by porcine epidemic diarrhea virus (PEDV). PED causes enteric disorders with an exceptionally high fatality in neonates, bringing substantial economic losses in the pork industry. The trimeric spike (S) glycoprotein of PEDV is responsible for virus-host recognition, membrane fusion, and is the main target for vaccine development and antigenic analysis. The atomic structures of the recombinant PEDV S proteins of two different strains have been reported, but they reveal distinct N-terminal domain 0 (D0) architectures that may correspond to different functional states. The existence of the D0 is a unique feature of alphacoronavirus. Here we combined cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to demonstrate in situ the asynchronous S protein D0 motions on intact viral particles of a highly virulent PEDV Pintung 52 strain. We further determined the cryo-EM structure of the recombinant S protein derived from a porcine cell line, which revealed additional domain motions likely associated with receptor binding. By integrating mass spectrometry and cryo-EM, we delineated the complex compositions and spatial distribution of the PEDV S protein N-glycans, and demonstrated the functional role of a key N-glycan in modulating the D0 conformation.
(© 2022. The Author(s).)
Databáze: MEDLINE
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