Fig. 7. Schematic diagram depicting refolding of acidified HA trimers in the proposed pathway from the initial neutral-pH form to a primed reversible form, followed by the irreversible transition to a final low-pH form. For the sake of simplicity, the receptors in the target membrane are not shown. The structure of the primed form is shown here as characterized at the neutral pH, and might be somewhat different at low pH. The membranes, HA1, the exposed FP and the kinked loop of HA2 are shown in brown, pink, green and blue, respectively. Exposure of the FP and kinked loop is reversible. In contrast, the dissociation of the HA1 trimer occurs already at the irreversible stage of HA refolding. The transition from primed to final form is promoted by interactions between adjacent trimers.