Fig. 6: Model of a successful membrane fusion event mediated by ATL.

Step I, monomeric ATLs sitting in two membranes generate Form 2-like loose crossover dimers upon GTP binding. Step II and II’, the 3HBs of ATL dimers are tightened by GTP hydrolysis to merge the two membranes. Self-association of the membrane-embedded helix formed by the linker region between the 3HB and TMD is required to transfer the energy gained from the conformational change in ATL to the membrane to complete fusion. Step III, the release of inorganic phosphate weakens the interaction between the GTPase ___domain and 3HB and activates the flexibility in the GTPase ___domain-3HB region of ATL, which exhibits a Form 1 conformational preference for dimer disassembly. Step IV, GDP release alters the conformational preference of monomeric ATL for the Form 2 or Form 3 conformation, getting ready for the next reaction cycle. GTP, GDP/Pi, and GDP are displayed as yellow, green, and blue spheres, respectively.