https://scholars.lib.ntu.edu.tw/handle/123456789/630688
標題: | Crystallographic and biophysical analysis of the fusion core from SARS-CoV-2 spike protein | 作者: | CHUN-HUA HSU | 關鍵字: | COVID-19 | fusion core | heptad repeat | SARS-CoV-2 | spike protein | 公開日期: | 1-一月-2023 | 來源出版物: | Journal of the Chinese Chemical Society | 摘要: | Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a newly emerging infectious pathogen causing coronavirus disease 2019 (COVID-19). The virus primarily infects cells via its spike glycoprotein, which is cleaved into S1 and S2 subunits to aid in cell attachment and membrane fusion, respectively. Heptad repeat 1 (HR1) and heptad repeat 2 (HR2) of the S2 subunit are essential for membrane fusion, culminating in an expected six-helix bundle termed fusion core. To better understand the structural and biophysical features of the SARS-CoV-2 fusion core, we designed, constructed, and bacterially produced a recombinant single-chain HR1-L6-HR2 protein and conducted a series of biochemical and biophysical experiments. Our findings demonstrate that the HR1-L6-HR2 protein spontaneously assembles into a highly stable trimeric complex, further confirmed by x-ray crystallographic analysis. The crystal structure of the fusion core reveals a trimeric coiled-coil structure of HR1 antiparallelly surrounded by three HR2 to form a six-helical bundle. Additionally, four residues of HR1 that contribute to binding with HR2 through the formation of hydrogen bonds and salt bridges were observed. These results indicate that the SARS-CoV-2 fusion core exhibits similar characteristics to other class I viral glycoproteins, suggesting potential for drug repurposing as an alternative strategy to combat COVID-19. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630688 | ISSN: | 00094536 | DOI: | 10.1002/jccs.202300124 |
顯示於: | 農業化學系 |
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