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Fig. 3 Schematic of the different steps in viral fusion. (a) Trimeric HA in the pre-fusion state (Wilson et al. 1981; PDB accession code 1HGG). HA is shown in yellow, HA2 in gray (two monomers) and in three different colors (third monomer). The transmembrane anchor is schematically shown as yellow ribbons, the cellular membrane in pink. The fusion peptide (red) is sequestered in the complex. (b) Only one monomer of HA2 is shown for clarity. The arrow indicates movement of the fusion peptide towards the cellular membrane after activation. (c) Hypothetical structure showing the HA2-monomer with the fusion peptide inserted into the cellular membrane just before refolding of HR2 (green) onto HR1 (blue).

(d) Refolding of HR2 and HR1 into the six-helix bundle brings the N-terminal fusion peptide and the C-terminal transmembrane anchor in close proximity, initiating hemi-fusion of the membranes.

(e) Complete fusion of the cellular with the viral membrane allows transfer of viral genetic material through the pore. The interaction of the fusion peptide with the transmembrane region of HA2 is hypothetical only (copyright Taylor & Francis Ltd, reproduced with permission from Schibli and Weissenhorn 2004)

and target membranes into sufficiently close apposition to initiate fusion according to the stalk hypothesis (Chernomordik and Kozlov 2005). The post-fusion state of the viral fusion protein is extremely stable, with unfolding temperatures >90°C (Baker et al. 1999). Hence, both the stability of coiled coils and their specificity are exploited in virus-induced membrane fusion.

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