Leash in the groove mechanism of membrane fusion.
Formation of helix bundles has been proposed as a general mechanism for viral and cellular membrane fusion reactions. Class I viral fusion proteins, including HIV Env and influenza hemagglutinin (HA), form six-helix bundles in their fusogenic forms. The HIV Env six-helix bundle extends to the membrane proximal end of the protein, where it is poised to pull the fusing membranes together. In contrast, the HA six-helix bundle is located at the membrane distal end of the protein. It is followed by a C-terminal 'leash' that packs into the grooves and extends to the membrane proximal end of the coiled-coil. Here, we describe the ability of C-terminal leash mutants to change conformation and induce fusion. Our data indicate that packing of the C-terminal leash into the grooves of the coiled-coil is necessary for HA to mediate the lipid mixing stage of fusion, and that hydrophobic membrane proximal leash residues secure this interaction. Therefore, HA employs a 'leash in the groove,' rather than a helix-bundle, mechanism of membrane fusion.
Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA.
Heather E
HE
Park
Jennifer A
JA
Gruenke
Judith M
JM
White
D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008561:Membrane Fusion / Q000502:physiology*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D014162:Transfection
D015699:HIV Envelope Protein gp120; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011994:Recombinant Proteins