title: Membrane-dependent conformation, dynamics, and lipid interactions of the fusion peptide of the paramyxovirus PIV5 from solid-state NMR.
abstract: The entry of enveloped viruses into cells requires protein-catalyzed fusion of the viral and cell membranes. The structure-function relation of a hydrophobic fusion peptide (FP) in viral fusion proteins is still poorly understood. We report magic-angle-spinning solid-state NMR results of the membrane-bound conformation, dynamics, and lipid interactions of the FP of the F protein of the paramyxovirus, parainfluenza virus 5 (PIV5). (13)C chemical shifts indicate that the PIV5 FP structure depends on the composition of the phospholipid membrane: the peptide is α-helical in palmitoyloleoylphosphatidylglycerol-containing anionic membranes but mostly β-sheet in neutral phosphocholine membranes. Other environmental factors, including peptide concentration, cholesterol, membrane reconstitution protocol, and a Lys solubility tag, do not affect the secondary structure. The α-helical and β-sheet states exhibit distinct dynamics and lipid interactions. The β-sheet FP is immobilized, resides on the membrane surface, and causes significant membrane curvature. In contrast, the α-helical FP undergoes intermediate-timescale motion and maintains the lamellar order of the membrane. Two-dimensional (31)P-(1)H correlation spectra show clear (31)P-water cross peaks for anionic membranes containing the α-helical FP but weak or no (31)P-water cross peak for neutral membranes containing the β-sheet FP. These results suggest that the β-sheet FP may be associated with high-curvature dehydrated fusion intermediates, while the α-helical state may be associated with the extended prehairpin state and the post-fusion state. Conformational plasticity is also a pronounced feature of the influenza and human immunodeficiency virus FPs, suggesting that these Gly-rich sequences encode structural plasticity to generate and sense different membrane morphologies.
authors.affiliation: Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yao
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism* / Q000821:virology*; D009682:Magnetic Resonance Spectroscopy; D008563:Membrane Lipids / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008563:Membrane Lipids; D014760:Viral Fusion Proteins