7y6u
Symmetry-expanded and locally refined protomer structure of IPEC-J2 cell-derived PEDV PT52 S with a CTD-close conformation
Structural highlights
FunctionA0A1Y0DD46_9ALPC S1 region attaches the virion to the cell membrane by interacting with the host receptor, initiating the infection. Binding to the receptor probably induces conformational changes in the S glycoprotein unmasking the fusion peptide of S2 region and activating membranes fusion. S2 region belongs to the class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04200] Publication Abstract from PubMedPorcine 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. In situ structure and dynamics of an alphacoronavirus spike protein by cryo-ET and cryo-EM.,Huang CY, Draczkowski P, Wang YS, Chang CY, Chien YC, Cheng YH, Wu YM, Wang CH, Chang YC, Chang YC, Yang TJ, Tsai YX, Khoo KH, Chang HW, Hsu SD Nat Commun. 2022 Aug 19;13(1):4877. doi: 10.1038/s41467-022-32588-3. PMID:35986008[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
