Myomerger Induces Membrane Hemifusion and Regulates Fusion Pore Expansion

• Published in: Biochemistry (Easton) 2024-03, Vol.63 (6), p.815-826
• Main Authors: Di Bartolo, Ary Lautaro, Caparotta, Marcelo, Polo, Luis Mariano, Masone, Diego
• Format: Article
• Language: English
• Subjects: Lipid Bilayers - metabolism; Membrane Fusion - physiology; Membrane Proteins - metabolism; Membranes - metabolism; Molecular Dynamics Simulation; Muscle Proteins - metabolism
• ISSN: 0006-2960; 1520-4995; 1520-4995
• DOI: 10.1021/acs.biochem.3c00682

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 much progress, cell–cell fusion has remained elusive to our understanding. Along the life of the fusion pore, large conformational changes take place from the initial lipid bilayer 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 the molecular level. In this work, we 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, reduces the nucleation–expansion energy difference, and promotes the formation of nonenlarging fusion pores.