Myomerger Induces Membrane Hemifusion and Regulates Fusion Pore Expansion

DI BARTOLO, ARY LAUTARO; CAPAROTTA, MARCELO; POLO, LUIS MARIANO; MASONE, DIEGO

Biochemistry

American Chemical Society

Año: 2024 vol. 63 p. 815 - 826

Membrane fusion is a crucial mechanism in a wide variety of important events in cell biology, from viral infection to exocytosis. However, despite many efforts and progress, cell-cell fusion has remained elusive to our understanding. Along the life of the fusionpore, large conformational changes take place from initial lipid bilayers bending, passing through the hemifusion intermediates and ending with the formation of the first nascent fusion pore. In this sense, computer simulations are an ideal technique for describing such complex lipid remodeling at molecular level. In this work, we have studied the role played by the muscle-specific membrane protein Myomerger during the formation of the fusion pore. We have conducted µs-length atomistic and coarse-grained molecular dynamics, together with free-energy calculations using ad hoc collective variables. Our results show that Myomerger favors the hemifusion diaphragm-stalk transition, reduce the nucleation-expansion energy difference and promotes the formation of non-enlarging fusion pores.