Structural biology of the influenza virus fusion peptide

• Authors: Remigiusz Worch
• Languages of publication: EN

Abstracts

EN

The release of influenza RNA inside the host cell occurs through the fusion of two membranes, the viral envelope and that of the cellular endosome. The fusion is mediated by the influenza hemagglutinin protein (HA), in particular by the fusion peptide (HAfp) located in the N-terminal fragment of HA2 subunit. This protein fragment anchors in the internal endosomal membrane, whereas the C-terminal HA2 part comprises a transmembrane domain (TMD) embedded in the viral envelope. A drop of pH in the endosome acts as the main trigger for HA2 large conformational change that leads to anchoring of the fusion peptide, close contact of the membranes and the subsequent fusion. Throughout the years the major research effort was focused on a 20-aminoacid fragment (HAfp1-20), shown by NMR to adopt a 'boomerang'-like structure. However, recent studies showed that extending HAfp1-20 by three highly conserved residues W21-Y22-G23 leads to formation of a unique, tight helical hairpin structure. This review summarizes recently discovered structural aspects of influenza fusion peptides and their relations with the membrane fusion mechanism.

Keywords

EN

influenza virus; viral entry; membrane fusion; fusion peptide; peptide-lipid interactions

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2014
• Volume: 61
• Issue: 3
• Pages: 421-426

Dates

published

2014

received

2014-05-30

revised

2014-08-14

accepted

2014-08-18

(unknown)

2014-09-08

Contributors

author

Remigiusz Worch

• Institute of Physics, Polish Academy of Sciences, Warsaw, Poland

References

• Apellániz B, Huarte N, Largo E, Nieva JL (2014) The three lives of viral fusion peptides. Chem Phys Lipids 181: 40-55.
• Chang DK, Cheng SF, Kantchev EA, Lin CH, Liu YT (2008) Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex. BMC Biol 6: 2.
• Chernomordik L V, Kozlov MM (2008) Mechanics of membrane fusion. Nat Struct Mol Biol 15: 675-683.
• Chernomordik L V, Zimmerberg J, Kozlov MM (2006) Membranes of the world unite! J. Cell Biol 175: 201-207.
• Colman PM, Lawrence MC (2003) The structural biology of type I viral membrane fusion. Nat Rev Mol Cell Biol 4: 309-319.
• Cross KJ, Langley WA, Russell RJ, Skehel JJ, Steinhauer DA (2009) Composition and functions of the influenza fusion peptide. Protein Pept Lett 16: 766-778.
• Donald JE, Zhang Y, Fiorin G, Carnevale V, Slochower DR, Gai F, Klein ML, DeGrado WF (2011) Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion. Proc Natl Acad Sci USA 108: 3958-3963.
• Du T, Jiang L, Liu M (2014) NMR structures of fusion peptide from influenza hemagglutinin H3 subtype and its mutants. J Pept Sci 20: 292-297.
• Epand R (2003) Fusion peptides and the mechanism of viral fusion. Biochim Biophys Acta -- Biomembr 1614: 116-121.
• Ghosh U, Xie L, Weliky DP (2013) Detection of closed influenza virus hemagglutinin fusion peptide structures in membranes by backbone (13)CO- (15)N rotational-echo double-resonance solid-state NMR. J Biomol NMR 55: 139-146.
• Harrison SC (2008) Viral membrane fusion. Nat Struct Mol Biol 15: 690-698.
• Jaroniec CP, Kaufman JD, Stahl SJ, Viard M, Blumenthal R, Wingfield PT, Bax A (2005) Structure and dynamics of micelle-associated human immunodeficiency virus gp41 fusion domain. Biochemistry 44: 16167-16180.
• Kim CS, Epand RF, Leikina E, Epand RM, Chernomordik LV (2011) The final conformation of the complete ectodomain of the HA2 subunit of influenza hemagglutinin can by itself drive low pH-dependent fusion. J Biol Chem 286: 13226-13234.
• Kleiger G, Grothe R, Mallick P, Eisenberg D (2002) GXXXG and AXXXA: common alpha-helical interaction motifs in proteins, particularly in extremophiles. Biochemistry 41: 5990-5997.
• Lai AL, Park H, White JM, Tamm LK (2006) Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity. J Biol Chem 281: 5760-5770.
• Lai AL, Tamm LK (2010) Shallow boomerang-shaped influenza hemagglutinin G13A mutant structure promotes leaky membrane fusion. J Biol Chem 285: 37467-37475.
• Langley WA, Thoennes S, Bradley KC, Galloway SE, Talekar GR, Cummings SF, Varecková E, Russell RJ, Steinhauer DA (2009) Single residue deletions along the length of the influenza HA fusion peptide lead to inhibition of membrane fusion function. Virology 394: 321-330.
• Larsson P, Kasson PM (2013) Lipid tail protrusion in simulations predicts fusogenic activity of influenza fusion peptide mutants and conformational models. PLoS Comput Biol 9: e1002950.
• Lee KK (2010) Architecture of a nascent viral fusion pore. EMBO J 29: 1299-1311.
• Li Y, Han X, Lai AL, Bushweller JH, Cafiso DS, Tamm LK (2005) Membrane structures of the hemifusion-inducing fusion peptide mutant G1S and the fusion-blocking mutant g1v of influenza virus hemagglutinin suggest a mechanism for pore opening in membrane fusion membrane structures of the hemifusion-inducing fusion pept. J Virol 79: 12065-12076.
• Lipari G, Szabo A (1982) Model-free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity. J Am Chem Soc 104: 4546-4559.
• Lorieau JL, Louis JM, Bax A (2010) The complete influenza hemagglutinin fusion domain adopts a tight helical hairpin arrangement at the lipid:water interface. Proc Natl Acad Sci USA 107: 11341-11346.
• Lorieau JL, Louis JM, Bax A (2011) Helical hairpin structure of influenza hemagglutinin fusion peptide. J Am Chem Soc 133: 2824-2827.
• Lorieau JL, Louis JM, Bax A (2013) The impact of influenza hemagglutinin fusion peptide length and viral subtype on its structure and dynamics. Biopolymers 99: 189-195.
• Lorieau JL, Louis JM, Schwieters CD, Bax A (2012) pH-triggered, activated-state conformations of the influenza hemagglutinin fusion peptide revealed by NMR. Proc Natl Acad Sci USA 109: 19994-19999.
• Luo M (2012) Influenza Virus Entry. In Viral Molecular Machines. Rossmann MG, Rao VB, eds, pp 201-221 Adv Exp Med Biol 726 Springer Science+Business Media, LLC 2012.
• Marsden HR, Tomatsu I, Kros A (2011) Model systems for membrane fusion. Chem Soc Rev 40: 1572-1585.
• Van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9: 112-124.
• Otterstrom J, van Oijen AM (2013) Visualization of membrane fusion, one particle at a time. Biochemistry 52: 1654-1668.
• Panahi A, Feig M (2010) Conformational sampling of influenza fusion peptide in membrane bilayers as a function of termini and protonation states. J Phys Chem B 114: 1407-1416.
• Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443: 651-657.
• Risselada HJ, Marelli G, Fuhrmans M, Smirnova YG (2012) Line-tension controlled mechanism for influenza fusion. PLoS One 7: 16-20.
• Russ WP, Engelman DM (2000) The GxxxG motif: a framework for transmembrane helix-helix association. J Mol Biol 296: 911-919.
• Schick M (2010) Membrane Fusion: the emergence of a new paradigm. J Stat Phys 142: 1317-1323.
• Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochemistry 69: 531-569.
• Sun Y, Weliky DP (2009) 13C-13C correlation spectroscopy of membrane-associated influenza virus fusion peptide strongly supports a helix-turn-helix motif and two turn conformations. J Am Chem Soc 131: 13228-13229.
• Tamm LK, Han X, Li Y, Lai AL (2002) Structure and function of membrane fusion peptides. Biopolymers 66: 249-260.
• Veit M (2012) Palmitoylation of virus proteins. Biol Cell 104: 493-515.
• Wasniewski CM, Parkanzky PD, Bodner ML, Weliky DP (2004) Solid-state nuclear magnetic resonance studies of HIV and influenza fusion peptide orientations in membrane bilayers using stacked glass plate samples. Chem Phys Lipids 132: 89-100.
• Wickner W, Schekman R (2008) Membrane fusion. Nat Struct Mol Biol 15: 658-664.
• Worch R (2013) The helical hairpin structure of the influenza fusion peptide can be seen on a hydrophobic moment map. FEBS Lett 587: 2980-2983.