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. 2021 Oct 1;434(6):167280. doi: 10.1016/j.jmb.2021.167280

Figure 2.

Figure 2

Molecular mechanism of Spike (S) protein-mediated virus-cell or cell–cell fusion. Top: the functional subdomains of the S protein. N-terminal domain (NTD), receptor binding domain (RBD), fusion peptide (FP), heptapeptide repeat sequences 1 and 2 (HR1 & HR2), transmembrane anchor (TA), C-terminal domain (CTD). Bottom: 1) The S protein associates with the ACE2 receptor via its RBD. It is also processed by cellular proteases at the S1/S2 or S2′ sites (not shown). 2) The S1 domain is released which allows for HR1 to extend and thrust the FP into the target cell plasma membrane. The FP anchors the target membrane while the TA anchors the fusion machinery to the viral or infected cell membrane. 3) Interactions between HR1 and HR2 results in a hairpin-like foldback that overcomes the energetic barrier to fusion and brings the membranes close together. A hemi-fusion step occurs where the outer layers of the fusing membranes merge (not shown). 4) The association of HR1 and HR2 and the corresponding membrane fusion result in the formation of a pore that will gradually expand. The viral or cytoplasmic contents are then merged.