๐ Identification of the fusion peptide-containing region in betacoronavirus spike glycoproteins
ยฉ 2016, American Society for Microbiology. The fusion peptides (FP) play an essential role in fusion of viral envelope with cellular membranes. The location and properties of the FPs in the spike (S) glycoproteins of different coronaviruses (CoV) have not yet been determined. Through amino acid sequence analysis of S proteins of representative Co. Vs, we identified a common region as a possible FP (pFP) that shares the characteristics of FPs of class I viral fusion proteins, including high Ala/Gly content, intermediate hydrophobicity, and few charged residues. To test the hypothesis that this region contains the CoV FP, we systemically mutated every residue in the pFP of Middle East respiratory syndrome betacoronavirus (MERS-CoV) and found that 11 of the 22 residues in the pFP (from G953 to L964, except for A956) were essential for S protein-mediated cell-cell fusion and virus entry. The synthetic MERS-CoV pFP core peptide (955IAGVGWTAGL964) induced extensive fusion of liposome membranes, while mutant peptide failed to induce any lipid mixing. We also selectively mutated residues in pFPs of two other ฮฒ-Co. Vs, severe acute respiratory syndrome coronavirus (SARS-CoV) and mouse hepatitis virus (MHV). Although the amino acid sequences of these two pFPs differed significantly from that of MERS-CoV and each other, most of the pFP mutants of SARS-CoV and MHV also failed to mediate membrane fusion, suggesting that these pFPs are also the functional FPs. Thus, the FPs of 3 different lineages of ฮฒ-Co. Vs are conserved in location within the S glycoproteins and in their functions, although their amino acid sequences have diverged significantly during CoV evolution.
keywords
๐ severe acute (1373)
๐ syndrome coronavirus (1074)
๐ cell-cell fusion (34)
๐ sequence analysis (118)
๐ hepatitis virus (437)
๐ acid sequence (108)
๐ amino acid (454)
๐ acid sequences (44)
๐ mouse hepatitis (371)
๐ fusion proteins (43)
๐ respiratory syndrome (2004)
๐ acute respiratory (1734)
๐ viral fusion (38)
๐ membrane fusion (105)
author
๐ค Ou, Xiuyuan
๐ค Zheng, Wangliang
๐ค Shan, Yiwei
๐ค Mu, Zhixia
๐ค Dominguez, Samuel R.
๐ค Holmes, Kathryn V.
๐ค Qian, Zhaohui
year
โฐ 2016
journal
๐ Journal of Virology
issn
๐ 10985514 0022538X
volume
90
number
12
page
5586-5600
citedbycount
11
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