Leash in the groove mechanism of membrane fusion.

Abstract

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.

• Authors: Heather E Park, Jennifer A Gruenke, Judith M White
• Journal: Nature structural biology (Nat Struct Biol) Vol. 10 Issue 12 Pg. 1048-53 (Dec 2003) ISSN: 1072-8368 [Print] United States
• PMID: 14595397 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• HIV Envelope Protein gp120
• Hemagglutinin Glycoproteins, Influenza Virus
• Recombinant Proteins

Topics

• Amino Acid Substitution
• Animals
• Cell Line
• Chlorocebus aethiops
• HIV Envelope Protein gp120 (chemistry, genetics)
• Hemagglutinin Glycoproteins, Influenza Virus (chemistry, genetics)
• Humans
• Kinetics
• Membrane Fusion (physiology)
• Models, Molecular
• Mutagenesis, Site-Directed
• Protein Conformation
• Recombinant Proteins (chemistry)
• Transfection