Model of spike-mediated membrane fusion showing peptide capture of fusion intermediates.
<p>Schematic of spike-mediated membrane fusion during virus infection. Full-length model of the spike glycoprotein from refs [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1012808#ppat.1012808.ref006" target="_blank">6</a>,<a hre...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , |
| منشور في: |
2025
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| الملخص: | <p>Schematic of spike-mediated membrane fusion during virus infection. Full-length model of the spike glycoprotein from refs [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1012808#ppat.1012808.ref006" target="_blank">6</a>,<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1012808#ppat.1012808.ref025" target="_blank">25</a>,<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1012808#ppat.1012808.ref064" target="_blank">64</a>] were used to highlight the HR1 (green) or HR2 (magenta) regions in the spike pre-fusion conformation. In the pre-fusion conformation (I), the RBD continuously samples the up and down conformations until it binds to ACE2 to form an ACE2-spike complex (II). ACE2 binding facilitates an open conformation (III, PDB ID 8Z7P) that exposes the HR1 and allows 3 trapping of the S2 intermediate by the 36-HR peptide. Formation of this intermediate occurs with displacement of the S1 subunit. The S2’ cleavage site is subsequently exposed to proteolysis by TMPRSS2 or other metalloproteases that allows trapping of a second S2’ fusion intermediate. The 36-HR peptide can trap either S2’ or S2’ fusion intermediate. The binding of the 36-HR2 peptide to the endogenous (viral) HR1 during transition to the fusion intermediate conformations interferes with formation of the endogenous six-helix bundle (IV, PDB ID 8FDW) preventing membrane fusion.</p> |
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