7cyd
From Proteopedia
Cryo-EM structures of Alphacoronavirus spike glycoprotein
Structural highlights
Function[SPIKE_CVH22] S1 region attaches the virion to the cell membrane by interacting with human ANPEP/aminopeptidase N, 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 (By similarity). Publication Abstract from PubMedCoronaviruses spike (S) glycoproteins mediate viral entry into host cells by binding to host receptors. However, how the S1 subunit undergoes conformational changes for receptor recognition has not been elucidated in Alphacoronavirus. Here, we report the cryo-EM structures of the HCoV-229E S trimer in prefusion state with two conformations. The activated conformation may pose the potential exposure of the S1-RBDs by decreasing of the interaction area between the S1-RBDs and the surrounding S1-NTDs and S1-RBDs compared to the closed conformation. Furthermore, structural comparison of our structures with the previously reported HCoV-229E S structure showed that the S trimers trended to open the S2 subunit from the closed conformation to open conformation, which could promote the transition from pre- to postfusion. Our results provide insights into the mechanisms involved in S glycoprotein-mediated Alphacoronavirus entry and have implications for vaccine and therapeutic antibody design. Cryo-EM analysis of the HCoV-229E spike glycoprotein reveals dynamic prefusion conformational changes.,Song X, Shi Y, Ding W, Niu T, Sun L, Tan Y, Chen Y, Shi J, Xiong Q, Huang X, Xiao S, Zhu Y, Cheng C, Fu ZF, Liu ZJ, Peng G Nat Commun. 2021 Jan 8;12(1):141. doi: 10.1038/s41467-020-20401-y. PMID:33420048[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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