Reovirus FAST Proteins Drive Pore Formation and Syncytiogenesis Using a Novel Helix-Loop-Helix Fusion-Inducing Lipid Packing Sensor

1. Boutilier J, Duncan R, editors. The reovirus fusion-associated small transmembrane (FAST) proteins: virus-encoded cellular fusogens. USA: Elsevier; 2011.

2. Ciechonska M, Duncan R. Reovirus FAST proteins: virus-encoded cellular fusogens. Trends Microbiol. 2014;22(12):715–24. doi: 10.1016/j.tim.2014.08.005 25245455

3. White JM, Delos SE, Brecher M, Schornberg K. Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Crit Rev Biochem Mol Biol. 2008;43(3):189–219. doi: 10.1080/10409230802058320 18568847

4. Corcoran JA, Duncan R. Reptilian reovirus utilizes a small type III protein with an external myristylated amino terminus to mediate cell-cell fusion. J Virol. 2004;78(8):4342–51. 15047847

5. Dawe S, Corcoran JA, Clancy EK, Salsman J, Duncan R. Unusual topological arrangement of structural motifs in the baboon reovirus fusion-associated small transmembrane protein. J Virol. 2005;79(10):6216–26. 15858006

6. Guo H, Sun X, Yan L, Shao L, Fang Q. The NS16 protein of aquareovirus-C is a fusion-associated small transmembrane (FAST) protein, and its activity can be enhanced by the nonstructural protein NS26. Virus Res. 2013;171(1):129–37. doi: 10.1016/j.virusres.2012.11.011 23201583

7. Racine T, Hurst T, Barry C, Shou J, Kibenge F, Duncan R. Aquareovirus effects syncytiogenesis by using a novel member of the FAST protein family translated from a noncanonical translation start site. J Virol. 2009;83(11):5951–5. doi: 10.1128/JVI.00171-09 19297495

8. Shmulevitz M, Duncan R. A new class of fusion-associated small transmembrane (FAST) proteins encoded by the non-enveloped fusogenic reoviruses. Embo J. 2000;19(5):902–12. 10698932

9. Thalmann CM, Cummins DM, Yu M, Lunt R, Pritchard LI, Hansson E, et al. Broome virus, a new fusogenic Orthoreovirus species isolated from an Australian fruit bat. Virology. 2010;402(1):26–40. doi: 10.1016/j.virol.2009.11.048 20350736

10. Albertini A, Bressanelli S, Lepault J, Gaudin Y. Structure and working of viral fusion machinery. Current topics in membranes. 2011;68 : 49–80. doi: 10.1016/B978-0-12-385891-7.00003-9 21771495

11. Brown CW, Stephenson KB, Hanson S, Kucharczyk M, Duncan R, Bell JC, et al. The p14 FAST protein of reptilian reovirus increases vesicular stomatitis virus neuropathogenesis. J Virol. 2009;83(2):552–61. doi: 10.1128/JVI.01921-08 18971262

12. Duncan R, Sullivan K. Characterization of two avian reoviruses that exhibit strain-specific quantitative differences in their syncytium-inducing and pathogenic capabilities. Virol. 1998;250 : 263–72.

13. Salsman J, Top D, Boutilier J, Duncan R. Extensive syncytium formation mediated by the reovirus FAST proteins triggers apoptosis-induced membrane instability J Virol. 2005;79(13):8090–100. 15956554

14. Zaitseva E, Mittal A, Griffin DE, Chernomordik LV. Class II fusion protein of alphaviruses drives membrane fusion through the same pathway as class I proteins. J Cell Biol. 2005;169(1):167–77. 15809312

15. Harrison SC. Viral membrane fusion. Nat Struct Mol Biol. 2008;15 : 690–8. doi: 10.1038/nsmb.1456 18596815

16. Melikyan GB. Common principles and intermediates of viral protein-mediated fusion: the HIV-1 paradigm. Retrovirology. 2008;5 : 111. doi: 10.1186/1742-4690-5-111 19077194

17. Chernomordik LV, Kozlov MM. Mechanics of membrane fusion. Nat Struct Mol Biol. 2008;15(7):675–83. doi: 10.1038/nsmb.1455 18596814

18. Kozlov MM, McMahon HT, Chernomordik LV. Protein-driven membrane stresses in fusion and fission. Trends Biochem Sci. 2010;35(12):699–706. 20638285. doi: 10.1016/j.tibs.2010.06.003

19. Ford MG, Mills IG, Peter BJ, Vallis Y, Praefcke GJ, Evans PR, et al. Curvature of clathrin-coated pits driven by epsin. Nature. 2002;419(6905):361–6. 12353027

20. Liu TY, Bian X, Sun S, Hu X, Klemm RW, Prinz WA, et al. Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion. Proc Natl Acad Sci U S A. 2012;109(32):E2146–54. doi: 10.1073/pnas.1208385109 22802620

21. Groffen AJ, Martens S, Diez Arazola R, Cornelisse LN, Lozovaya N, de Jong AP, et al. Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release. Science. 2010;327(5973):1614–8. doi: 10.1126/science.1183765 20150444

22. Martens S, Kozlov MM, McMahon HT. How synaptotagmin promotes membrane fusion. Science. 2007;316(5828):1205–8. 17478680

23. Vamparys L, Gautier R, Vanni S, Bennett WF, Tieleman DP, Antonny B, et al. Conical lipids in flat bilayers induce packing defects similar to that induced by positive curvature. Biophys J. 2013;104(3):585–93. doi: 10.1016/j.bpj.2012.11.3836 23442909

24. McMahon HT, Kozlov MM, Martens S. Membrane curvature in synaptic vesicle fusion and beyond. Cell. 2010;140(5):601–5. doi: 10.1016/j.cell.2010.02.017 20211126

25. Chernomordik LV, Zimmerberg J, Kozlov MM. Membranes of the world unite! J Cell Biol. 2006;175(2):201–7. 17043140

26. Cohen FS, Melikyan GB. The energetics of membrane fusion from binding, through hemifusion, pore formation, and pore enlargement. J Membr Biol. 2004;199(1):1–14. 15366419

27. Chernomordik LV, Kozlov MM. Protein-lipid interplay in fusion and fission of biological membranes. Annu Rev Biochem. 2003;72 : 175–207. 14527322

28. Reese C, Mayer A. Transition from hemifusion to pore opening is rate limiting for vacuole membrane fusion. J Cell Biol. 2005;171(6):981–90. 16365164

29. Parmar HB, Barry C, Kai F, Duncan R. Golgi complex-plasma membrane trafficking directed by an autonomous, tribasic Golgi export signal. Mol Biol Cell. 2014;25(6):866–78. doi: 10.1091/mbc.E13-07-0364 24451258

30. Dawe S, and R. Duncan. The S4 genome segment of baboon reovirus is bicistronic and encodes a novel fusion-associated small transmembrane protein. J Virol. 2002;76 : 2131–40. 11836390

31. Shmulevitz M, Salsman J, Duncan R. Palmitoylation, membrane-proximal basic residues, and transmembrane glycine residues in the reovirus p10 protein are essential for syncytium formation. J Virol. 2003;77(18):9769–79. 12941885

32. Barry C, Duncan R. Multifaceted sequence-dependent and-independent roles for reovirus FAST protein cytoplasmic tails in fusion pore formation and syncytiogenesis. J Virol. 2009;83(23):12185–95. 19759162. doi: 10.1128/JVI.01667-09

33. Clancy EK, Duncan R. Reovirus FAST protein transmembrane domains function in a modular, primary sequence-independent manner to mediate cell-cell membrane fusion. J Virol. 2009;83(7):2941–50. doi: 10.1128/JVI.01869-08 19129451

34. Clancy EK, Duncan R. Helix-destabilizing, beta-branched, and polar residues in the baboon reovirus p15 transmembrane domain influence the modularity of FAST proteins. J Virol. 2011;85(10):4707–19. doi: 10.1128/JVI.02223-10 21367887

35. Barry C, Key T, Haddad R, Duncan R. Features of a spatially constrained cystine loop in the p10 FAST protein ectodomain define a new class of viral fusion peptide. J Biol Chem. 2010;285(22):16424–33. doi: 10.1074/jbc.M110.118232 20363742

36. Corcoran JA, Syvitski R, Top D, Epand RM, Epand RF, Jakeman D, et al. Myristoylation, a protruding loop, and structural plasticity are essential features of a nonenveloped virus fusion peptide motif. J Biol Chem. 2004;279(49):51386–94. 15448165

37. Key T, Duncan R. A compact, multifunctional fusion module directs cholesterol-dependent homomultimerization and syncytiogenic efficiency of reovirus p10 FAST proteins. PLoS Pathog. 2014;10:e1004023. doi: 10.1371/journal.ppat.1004023 24651689

38. Top D, Read JA, Dawe SJ, Syvitski RT, Duncan R. Cell-cell membrane fusion induced by p15 fusion-associated small transmembrane (FAST) protein requires a novel fusion peptide motif containing a myristoylated polyproline type II helix. J Biol Chem. 2012;287(5):3403–14. doi: 10.1074/jbc.M111.305268 22170056

39. Cortese MS, Uversky VN, Dunker AK. Intrinsic disorder in scaffold proteins: getting more from less. Prog Biophys Mol Biol. 2008;98(1):85–106. doi: 10.1016/j.pbiomolbio.2008.05.007 18619997

40. Ciechonska M, Duncan R. Efficient reovirus -⁠ and measles virus-mediated pore expansion during syncytium formation is dependent on annexin A1 and intracellular calcium. J Virol. 2014;88 : 6137–47. doi: 10.1128/JVI.00121-14 24648446

41. Top D, Barry C, Racine T, Ellis CL, Duncan R. Enhanced fusion pore expansion mediated by the trans-acting Endodomain of the reovirus FAST proteins. PLoS Pathog. 2009;5(3):e1000331. doi: 10.1371/journal.ppat.1000331 19266079

42. Key T, Sarker M, de Antueno R, Rainey JK, Duncan R. The p10 FAST protein fusion peptide functions as a cystine noose to induce cholesterol-dependent liposome fusion without liposome tubulation. Biochim Biophys Acta. 2015;1848(2):408–16. doi: 10.1016/j.bbamem.2014.10.020 25450808

43. Shmulevitz M, Epand RF, Epand RM, Duncan R. Structural and functional properties of an unusual internal fusion peptide in a nonenveloped virus membrane fusion protein. J Virol. 2004;78 : 2808–18. 14990700

44. Kelley LA, Sternberg MJ. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc. 2009;4(3):363–71. doi: 10.1038/nprot.2009.2 19247286

45. Wuthrich K. NMR of proteins and nucleic acids. New York: John Wiley & Sons; 1986.

46. Ding J, Rainey JK, Xu C, Sykes BD, Fliegel L. Structural and functional characterization of transmembrane segment VII of the Na+/H+ exchanger isoform 1. J Biol Chem. 2006;281(40):29817–29. 16861220

47. Bigay J, Casella JF, Drin G, Mesmin B, Antonny B. ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif. Embo J. 2005;24(13):2244–53. 15944734

48. Drin G, Antonny B. Amphipathic helices and membrane curvature. FEBS Lett. 2010;584(9):1840–7. doi: 10.1016/j.febslet.2009.10.022 19837069

49. Antonny B. Mechanisms of membrane curvature sensing. Annu Rev Biochem. 2011;80 : 101–23. doi: 10.1146/annurev-biochem-052809-155121 21438688

50. Eisenberg D, Weiss RM, Terwilliger TC. The hydrophobic moment detects periodicity in protein hydrophobicity. Proc Natl Acad Sci U S A. 1984;81(1):140–4. 6582470

51. Levi S, Rawet M, Kliouchnikov L, Parnis A, Cassel D. Topology of amphipathic motifs mediating Golgi localization in ArfGAP1 and its splice isoforms. J Biol Chem. 2008;283(13):8564–72. doi: 10.1074/jbc.M709738200 18195007

52. Gonzalez-Rubio P, Gautier R, Etchebest C, Fuchs PF. Amphipathic-Lipid-Packing-Sensor interactions with lipids assessed by atomistic molecular dynamics. Biochim Biophys Acta. 2011;1808(9):2119–27. doi: 10.1016/j.bbamem.2011.05.006 21600869

53. Fernandes F, Loura LM, Chichon FJ, Carrascosa JL, Fedorov A, Prieto M. Role of helix 0 of the N-BAR domain in membrane curvature generation. Biophys J. 2008;94(8):3065–73. doi: 10.1529/biophysj.107.113118 18199667

54. Lee MT, Hung WC, Chen FY, Huang HW. Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides. Proc Natl Acad Sci U S A. 2008;105(13):5087–92. doi: 10.1073/pnas.0710625105 18375755

55. Lenarcic R, Halbedel S, Visser L, Shaw M, Wu LJ, Errington J, et al. Localisation of DivIVA by targeting to negatively curved membranes. EMBO J. 2009;28(15):2272–82. doi: 10.1038/emboj.2009.129 19478798

56. Leikina E, LeDuc DL, Macosko JC, Epand R, Shin YK, Chernomordik LV. The 1–127 HA2 construct of influenza virus hemagglutinin induces cell-cell hemifusion. Biochemistry. 2001;40(28):8378–86. 11444985

57. Chernomordik LV, Zimmerberg J. Bending membranes to the task: structural intermediates in bilayer fusion. Curr Opin Struct Biol. 1995;5(4):541–7. 8528771

58. Leikina E, Chernomordik LV. Reversible merger of membranes at the early stage of influenza hemagglutinin-mediated fusion. Mol Biol Cell. 2000;11(7):2359–71. 10888674

59. Clancy EK, Barry C, Ciechonska M, Duncan R. Different activities of the reovirus FAST proteins and influenza hemagglutinin in cell-cell fusion assays and in response to membrane curvature agents. Virology. 2010;397(1):119–29. doi: 10.1016/j.virol.2009.10.039 19931884

60. Vanni S, Vamparys L, Gautier R, Drin G, Etchebest C, Fuchs PF, et al. Amphipathic lipid packing sensor motifs: probing bilayer defects with hydrophobic residues. Biophys J. 2013;104(3):575–84. doi: 10.1016/j.bpj.2012.11.3837 23442908

61. Parton RG, Hanzal-Bayer M, Hancock JF. Biogenesis of caveolae: a structural model for caveolin-induced domain formation. J Cell Sci. 2006;119(Pt 5):787–96.

62. Lorieau JL, Louis JM, Bax A. The complete influenza hemagglutinin fusion domain adopts a tight helical hairpin arrangement at the lipid:water interface. Proc Natl Acad Sci U S A. 2010;107(25):11341–6. doi: 10.1073/pnas.1006142107 20534508

63. Rozenberg-Adler Y, Conner J, Aguilar-Carreno H, Chakraborti S, Dimitrov DS, Anderson WF. Membrane-proximal cytoplasmic domain of Moloney murine leukemia virus envelope tail facilitates fusion. Exp Mol Pathol. 2008;84(1):18–30. doi: 10.1016/j.yexmp.2007.11.001 18222422

64. Cathomen T, Naim HY, Cattaneo R. Measles viruses with altered envelope protein cytoplasmic tails gain cell fusion competence. J Virol. 1998;72(2):1224–34. 9445022

65. Lin X, Derdeyn CA, Blumenthal R, West J, Hunter E. Progressive truncations C terminal to the membrane-spanning domain of simian immunodeficiency virus Env reduce fusogenicity and increase concentration dependence of Env for fusion. J Virol. 2003;77(12):7067–77. 12768026

66. Melikyan GB, Markosyan RM, Brener SA, Rozenberg Y, Cohen FS. Role of the cytoplasmic tail of ecotropic moloney murine leukemia virus Env protein in fusion pore formation. J Virol. 2000;74(1):447–55. 10590134

67. Epand RF, Zhang YL, Mirzabekov T, Kagan B, Silberstein A, Hubbell WL, et al. Membrane activity of an amphiphilic alpha-helical membrane-proximal cytoplasmic domain of the MoMuLV envelope glycoprotein. Exp Mol Pathol. 2008;84(1):9–17. doi: 10.1016/j.yexmp.2007.11.003 18206141

68. Dutch RE, Lamb RA. Deletion of the cytoplasmic tail of the fusion protein of the paramyxovirus simian virus 5 affects fusion pore enlargement. J Virol. 2001;75(11):5363–9. 11333918

69. Kozerski C, Ponimaskin E, Schroth-Diez B, Schmidt MF, Herrmann A. Modification of the cytoplasmic domain of influenza virus hemagglutinin affects enlargement of the fusion pore. J Virol. 2000;74(16):7529–37. 10906206

70. Richard JP, Leikina E, Langen R, Henne WM, Popova M, Balla T, et al. Intracellular curvature-generating proteins in cell-to-cell fusion. Biochem J. 2011;440(2):185–93. doi: 10.1042/BJ20111243 21895608

71. Trouillon R, Ewing AG. Amperometric measurements at cells support a role for dynamin in the dilation of the fusion pore during exocytosis. Chemphyschem: a European journal of chemical physics and physical chemistry. 2013;14(10):2295–301. doi: 10.1002/cphc.201300319 23824748.

72. Antin PB, Ordahl CP. Isolation and characterization of an avian myogenic cell line. Dev Biol. 1991;143(1):111–21. 1985013

73. Top D, de Antueno R, Salsman J, Corcoran J, Mader J, Hoskin D, et al. Liposome reconstitution of a minimal protein-mediated membrane fusion machine. EMBO J. 2005;24(17):2980–8. 16079913

74. Heckman KL, Pease LR. Gene splicing and mutagenesis by PCR-driven overlap extension. Nat Protoc. 2007;2(4):924–32. 17446874

75. Sohma Y, Taniguchi A, Yoshiya T, Chiyomori Y, Fukao F, Nakamura S, et al. 'Click peptide': a novel 'O-acyl isopeptide method' for peptide synthesis and chemical biology-oriented synthesis of amyloid beta peptide analogues. J Pept Sci. 2006;12(12):823–8. 17131295

76. Schwieters CD, Kuszewski JJ, Tjandra N, Clore GM. The Xplor-NIH NMR molecular structure determination package. J Magn Reson. 2003;160(1):65–73. 12565051

77. Kuszewski J, Gronenborn AM, Clore GM. Improvements and extensions in the conformational database potential for the refinement of NMR and X-ray structures of proteins and nucleic acids. J Magn Reson. 1997;125(1):171–7. 9245376