The energetics of membrane fusion from binding, through hemifusion, pore formation, and pore enlargement

Abstract

The main steps of viral membrane fusion are local membrane approach, hemifusion, pore formation, and pore enlargement. Experiments and theoretical analyses have helped determine the relative energies required for each step. Key protein structures and conformational changes of the fusion process have been identified. The physical deformations of monolayer bending and lipid tilt have been applied to the steps of membrane fusion. Experiment and theory converge to strongly indicate that, contrary to former conceptions, the fusion process is progressively more energetically difficult: hemifusion has a relatively low energy barrier, pore formation is more energy-consuming, and pore enlargement is the most difficult to achieve.