Curvature Sensing by a Viral Scission Protein.
Membrane scission is the final step in all budding processes wherein a membrane neck is sufficiently constricted so as to allow for fission and the release of the budded particle. For influenza viruses, membrane scission is mediated by an amphipathic helix (AH) domain in the viral M2 protein. While it is known that the M2AH alters membrane curvature, it is not known how the protein is localized to the center neck of budding virions where it would be able to cause membrane scission. Here, we use molecular dynamics simulations on buckled lipid bilayers to show that the M2AH senses membrane curvature and preferentially localizes to regions of high membrane curvature, comparable to that seen at the center neck of budding influenza viruses. These results were then validated using in vitro binding assays to show that the M2AH senses membrane curvature by detecting lipid packing defects in the membrane. Our results show that the M2AH senses membrane curvature and suggest that the AH domain may localize the protein at the viral neck where it can then mediate membrane scission and the release of budding viruses.
School of Biosciences, University of Kent , Canterbury, Kent CT2 7NJ, United Kingdom.
Agnieszka
A
Martyna
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University , SE-106 91 Stockholm, Sweden.
Jordi
J
Gómez-Llobregat
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University , SE-106 91 Stockholm, Sweden.
Martin
M
Lindén
School of Biosciences, University of Kent , Canterbury, Kent CT2 7NJ, United Kingdom.
Jeremy S
JS
Rossman
D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism*; D057074:Virus Release / Q000502:physiology*
D008051:Lipid Bilayers; D008563:Membrane Lipids; D014763:Viral Matrix Proteins