Membrane remodeling by the M2 amphipathic helix drives influenza virus membrane scission.
Membrane scission is a crucial step in all budding processes, from endocytosis to viral budding. Many proteins have been associated with scission, though the underlying molecular details of how scission is accomplished often remain unknown. Here, we investigate the process of M2-mediated membrane scission during the budding of influenza viruses. Residues 50-61 of the viral M2 protein bind membrane and form an amphipathic α-helix (AH). Membrane binding requires hydrophobic interactions with the lipid tails but not charged interactions with the lipid headgroups. Upon binding, the M2AH induces membrane curvature and lipid ordering, constricting and destabilizing the membrane neck, causing scission. We further show that AHs in the cellular proteins Arf1 and Epsin1 behave in a similar manner. Together, they represent a class of membrane-induced AH domains that alter membrane curvature and fluidity, mediating the scission of constricted membrane necks in multiple biological pathways.
School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
Agnieszka
A
Martyna
School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
Basma
B
Bahsoun
School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
Matthew D
MD
Badham
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA.
Saipraveen
S
Srinivasan
School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
Mark J
MJ
Howard
School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom.
Jeremy S
JS
Rossman
D000595:Amino Acid Sequence; D057927:Hydrophobic and Hydrophilic Interactions; D008567:Membranes, Artificial; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000648:ultrastructure; D000086082:Viroporin Proteins
D008567:Membranes, Artificial; D010455:Peptides; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins