title: Structural features of fusogenic model transmembrane domains that differentially regulate inner and outer leaflet mixing in membrane fusion.
abstract: The transmembrane domains of fusion proteins are known to be important for their fusogenic activity. In an effort to systematically investigate the structure/function relationships of transmembrane domains we had previously designed LV-peptides that mimic natural fusion protein TMDs in their ability to drive fusion after incorporation into liposomal membranes. Here, we investigate the impact of different structural features of LV-peptide TMDs on inner and outer leaflet mixing. We find that fusion driven by the helical peptides involves a hemifusion intermediate as previously seen for natural fusion proteins. Helix backbone dynamics enhances fusion by selectively promoting outer leaflet mixing. Furthermore, the hydrophobic length of the peptides as well as covalent attachment of long acyl chains affects outer and inner leaflet mixing to different extents. Different structural features of transmembrane domains thus appear to differentially influence the rearrangements of lipids in fusion initiation and the hemifusion-to-fusion transition. The relevance of these findings in respect to the function of natural fusion proteins is discussed.
authors: Lehrstuhl Chemie der Biopolymere, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising, and Munich Center for Integrated Protein Science (CIPSM), Germany.
authors: Bernhard C
authors: BC
authors: Poschner
authors: Konrad
authors: K
authors: Fischer
authors: Jana R
authors: JR
authors: Herrmann
authors: Mathias W
authors: MW
authors: Hofmann
authors: Dieter
authors: D
authors: Langosch
mesh_terms: D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008561:Membrane Fusion; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D050600:SNARE Proteins / Q000737:chemistry* / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008081:Liposomes; D010455:Peptides; D050600:SNARE Proteins; D014764:Viral Proteins