Filamentous Bacteriophage Proteins and Assembly

  • Suzana K. StrausEmail author
  • Htet E. Bo
Part of the Subcellular Biochemistry book series (SCBI, volume 88)


Filamentous bacteriophages, also known as filamentous bacterial viruses or Inoviruses, have been studied extensively over the years. They are interesting paradigms in structural molecular biology and offer insight into molecular assembly, a process that remains to be fully understood. In this chapter, an overview on filamentous bacteriophages will be provided. In particular, we review the constituent proteins of filamentous bacteriophage and discuss assembly by examining the structure of the major coat protein at various stages of the process. The minor coat proteins will also be briefly reviewed. Structural information provides key snapshots into the dynamic process of assembly.


Inovirus Macromolecular assembly Major coat protein Minor coat proteins 



We would like to thank Dr. Walter Scott for carefully reading through the manuscript and providing constructive criticism. We would also like to thank Dr. Don A. Marvin for a wonderful collaboration and for teaching us all we know about filamentous bacteriophage. This chapter is a “lighter” version of our more in-depth review (Marvin et al. 2014), which we invite you to dive into for further details. Finally, funding from the Natural Sciences and Engineering Research Council of Canada is acknowledged.


  1. Abramov G, Morag O, Goldbourt A (2015) Magic-angle spinning NMR of intact bacteriophages: insights into the capsid, DNA and their interface. J Magn Reson 253:80–90. Scholar
  2. Adams MC, Belcher A, Keck WM, Grossman JC (2013) Highly-conductive cathode for lithium-ion battery using M13 phage - SWCNT complexGoogle Scholar
  3. Almeida FCL, Opella SJ (1997) Fd coat protein structure in membrane environments: structural dynamics of the loop between the hydrophobic trans-membrane helix and the amphipathic in-plane helix. J Mol Biol 270:481–495. Scholar
  4. Amako K, Yasunaka K (1977) Ether induced morphological alteration of Pf-1 filamentous phage. Nature 267:862–863CrossRefGoogle Scholar
  5. Anany H, Chou Y, Cucic S et al (2017) From bits and pieces to whole phage to Nanomachines: pathogen detection using bacteriophages. Annu Rev Food Sci Technol 8:305–329. Scholar
  6. Bawono P, Heringa J (2014) PRALINE: a versatile multiple sequence alignment toolkit. Methods Mol Biol 1079:245–262CrossRefGoogle Scholar
  7. Bradley DE (1964) The structure of some bacteriophages associated with male strains of Escherichia Coli. J Gen Microbiol 35:471–482. Scholar
  8. Briegel A, Ortega DR, Tocheva EI et al (2009) Universal architecture of bacterial chemoreceptor arrays. Proc Natl Acad Sci 106:17181–17186. Scholar
  9. Burnell E, Alphen L, Van VA, De KB (1980) 31P nuclear magnetic resonance and freeze-fracture electron microscopy studies on escherichia coli. Biochim Biophys Acta 597:492–501CrossRefGoogle Scholar
  10. Caspar DL, Makowski L (1981) The symmetries of filamentous phage particles. J Mol Biol 145:611–617CrossRefGoogle Scholar
  11. Chopin MC, Rouault A, Dusko Ehrlich S, Gautier M (2002) Filamentous phage active on the gram-positive bacterium Propionibacterium freudenreichii. J Bacteriol 184:2030–2033. Scholar
  12. Criscuolo E, Spadini S, Lamanna J et al (2017) Bacteriophages and their immunological applications against infectious threats. J Immunol Res 2017:1–13. Scholar
  13. Cross TA, Opella SJ (1980) Structural properties of fd coat protein in sodium dodecyl sulfate micelles. Biochem Biophys Res Commun 92:478–484CrossRefGoogle Scholar
  14. Cross TA, Opella SJ (1982) Protein dynamics by solid-state nuclear magnetic resonance spectroscopy. Peptide backbone of the coat protein in fd bacteriophage. J Mol Biol 159:543–549CrossRefGoogle Scholar
  15. Cross TA, Gall CM, Opella SJ (1981) NMR studies of filamentous bacteriophage assembly. Prog Clin Biol Res 64:457–465PubMedGoogle Scholar
  16. Cross TA, Tsang P, Opella SJ (1983) Comparison of protein and deoxyribonucleic acid backbone structures in fd and Pf1 bacteriophages. Biochemistry 22:721–726CrossRefGoogle Scholar
  17. Cross TA, Sharma M, Yi M, Zhou H-X (2011) Influence of solubilizing environments on membrane protein structures. Trends Biochem Sci 36:117–125. Scholar
  18. Day LA (1966) Protein conformation in fd bacteriophage as investigated by optical rotatory dispersion. J Mol Biol 15:395–398CrossRefGoogle Scholar
  19. Gagic D, Ciric M, Wen WX et al (2016) Exploring the secretomes of microbes and microbial communities using filamentous phage display. Front Microbiol 7:1–19. Scholar
  20. Glaser-Wuttke G, Keppner J, Rasched I (1989) Pore-forming properties of the adsorption protein of filamentous phage fd. Biochim Biophys Acta 985:239–247CrossRefGoogle Scholar
  21. Goldbourt A, Gross BJ, Day LA, McDermott AE (2007) Filamentous phage studied by magic-angle spinning NMR: resonance assignment and secondary structure of the coat protein in Pf1. J Am Chem Soc 129:2338–2344. Scholar
  22. Goldbourt A, Day LA, McDermott AE (2010) Intersubunit hydrophobic interactions in Pf1 filamentous phage. J Biol Chem 285:37051–37059. Scholar
  23. Griffith J, Manning M, Dunn K (1981) Filamentous bacteriophage contract into hollow spherical particles upon exposure to a chloroform-water interface. Cell 23:747–753CrossRefGoogle Scholar
  24. Hemminga MA, Vos WL, Nazarov PV et al (2010) Viruses: incredible nanomachines. New advances with filamentous phages. Eur Biophys J 39:541–550. Scholar
  25. Henry GD, Sykes BD (1990) Detergent-solubilized M13 coat protein exists as an asymmetric dimer. J Mol Biol 212:11–14. Scholar
  26. Henry GD, Sykes BD (1992) Assignment of amide 1H and 15N NMR resonances in detergent-solubilized M13 coat protein: a model for the coat protein dimer. Biochemistry 31:5284–5297CrossRefGoogle Scholar
  27. Hofmann-Berling H, Marvin DA, Duerwald H (1963) A filamentous DNA phage (fd) and a spherical RNA phage (fr), host-specific for the male strain of E. Coli. 1. Preparation and chemical properties of fd and fr. Zeitschrift fur Naturforschung Tl B, Chemie, Biochem Biophys Biol und verwandte Gebiete 18:876–883Google Scholar
  28. Hofschneider P (1963) Untersuchungen über “kleine” E. coli K12 Bacteriophagen. 1 und 2 Mitteilung. Z Naturforsch 18b:203–205CrossRefGoogle Scholar
  29. Hunter GJ, Rowitch DH, Perham RN (1987) Interactions between DNA and coat protein in the structure and assembly of filamentous bacteriophage fd. Nature 327:252–254. Scholar
  30. Käll L, Krogh A, Sonnhammer EL (2004) A combined transmembrane topology and signal peptide prediction method. J Mol Biol 338:1027–1036. Scholar
  31. Karlsson F, Borrebaeck CA, Nilsson N (2003) The mechanism of bacterial infection by filamentous phages involves molecular interactions between TolA and phage protein 3 domains the mechanism of bacterial infection by filamentous phages involves molecular interactions between TolA and phage protein 3. J Bacteriol 185:2628–2634. Scholar
  32. Krogh A, Larsson B, von Heijne G, Sonnhammer EL (2001) Predicting transmembrane protein topology with a hidden markov model: application to complete genomes11. Edited by F. Cohen. J Mol Biol 305:567–580. Scholar
  33. Loeb T, Zinder ND (1961) A Bacteriophage containing RNA. Proc Natl Acad Sci U S A 47:282–289. Scholar
  34. Lomize AL, Pogozheva ID, Lomize MA, Mosberg HI (2006a) Positioning of proteins in membranes: a computational approach. Protein Sci 15:1318–1333. Scholar
  35. Lomize MA, Lomize AL, Pogozheva ID, Mosberg HI (2006b) OPM: orientations of proteins in membranes database. Bioinformatics 22:623–625. Scholar
  36. Lomize MA, Pogozheva ID, Joo H et al (2012) OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res 40:D370–D376. Scholar
  37. Lopez J, Webster RE (1982) Minor coat protein composition and location of the a protein in bacteriophage f1 spheroids and I-forms. J Virol 42:1099–1107PubMedPubMedCentralGoogle Scholar
  38. Lopez J, Webster RE (1983) Morphogenesis of filamentous bacteriophage f1: orientation of extrusion and production of polyphage. Virology 127:177–193CrossRefGoogle Scholar
  39. Manning M, Griffith J (1985) Association of M13 I-forms and spheroids with lipid vesicles. Arch Biochem Biophys 236:297–303CrossRefGoogle Scholar
  40. Marvin DA (1966) X-ray diffraction and electron microscope studies on the structure of the small filamentous bacteriophage fd. J Mol Biol 15:8–17CrossRefGoogle Scholar
  41. Marvin DA (1998) Filamentous phage structure, infection and assembly. Curr Opin Struct Biol 8:150–158CrossRefGoogle Scholar
  42. Marvin DA (2017) Fibre diffraction studies of biological macromolecules. Prog Biophys Mol Biol 127:43–87CrossRefGoogle Scholar
  43. Marvin DA, Hoffmann-Berling H (1963a) Physical and chemical properties of two new small bacteriophages. Nature 197:517–518. Scholar
  44. Marvin DA, Hoffmann-Berling H (1963b) A fibrous DNA phage (fd) AND a spherical RNA phage (fr) specific for male strains of E. Coli. II Physical characteristics. Zeitschrift fur Naturforschung Tl B, Chemie, Biochem Biophys Biol und verwandte Gebiete 18:884–893Google Scholar
  45. Marvin DA, Wachtel EJ (1976) Structure and assembly of filamentous bacterial viruses. Philos Trans R Soc Lond Ser B Biol Sci 276:81–98CrossRefGoogle Scholar
  46. Marvin DA, Wiseman RL, Wachtel EJ (1974) Filamentous bacterial viruses. XI. Molecular architecture of the class II (Pf1, Xf) virion. J Mol Biol 82:121–138CrossRefGoogle Scholar
  47. Marvin DA, Welsh LC, Symmons MF et al (2006) Molecular structure of fd (f1, M13) filamentous Bacteriophage refined with respect to X-ray fibre diffraction and solid-state NMR data supports specific models of phage assembly at the bacterial membrane. J Mol Biol 355:294–309. Scholar
  48. Marvin DA, Symmons MF, Straus SK (2014) Structure and assembly of filamentous bacteriophages. Prog Biophys Mol Biol 114:80–122. Scholar
  49. Morag O, Sgourakis NG, Baker D, Goldbourt A (2015) The NMR–Rosetta capsid model of M13 bacteriophage reveals a quadrupled hydrophobic packing epitope. Proc Natl Acad Sci 112:971–976. Scholar
  50. Nave C, Fowler AG, Malsey S et al (1979) Macromolecular structural transitions in Pf1 filamentous bacterial virus. Nature 281:232–234CrossRefGoogle Scholar
  51. Nazarov PV, Koehorst RBM, Vos WL et al (2007) FRET study of membrane proteins: determination of the tilt and orientation of the N-terminal domain of M13 major coat protein. Biophys J 92:1296–1305. Scholar
  52. Opella SJ, Zeri AC, Park SH (2008) Structure, dynamics, and assembly of filamentous bacteriophages by nuclear magnetic resonance spectroscopy. Annu Rev Phys Chem 59:635–657. Scholar
  53. Papavoine CHM, Christiaans BEC, Folmer RHA et al (1998) Solution structure of the M13 major coat protein in detergent micelles: a basis for a model of phage assembly involving specific residues. J Mol Biol 282:401–419. Scholar
  54. Pederson DM, Welsh LC, Marvin DA et al (2001) The protein capsid of filamentous bacteriophage PH75 from Thermus thermophilus. J Mol Biol 309:401–421. Scholar
  55. Quinn CM, Polenova T (2017) Structural biology of supramolecular assemblies by magic-angle spinning NMR spectroscopy. Q Rev Biophys 50:e1. Scholar
  56. Russel M (1991) Filamentous phage assembly. Mol Microbiol 5:1607–1613CrossRefGoogle Scholar
  57. Russel M, Model P (2006) Filamentous Phage. In: Calendar R (ed) The bacteriophages, 2nd edn. Oxford University Press, Oxford, UK, pp 146–160Google Scholar
  58. Russel M, Linderoth NA, Šali A (1997) Filamentous phage assembly: variation on a protein export theme. Gene 192:23–32. Scholar
  59. Sergeyev IV, Itin B, Rogawski R et al (2017) Efficient assignment and NMR analysis of an intact virus using sequential side-chain correlations and DNP sensitization. Proc Natl Acad Sci 114:5171–5176. Scholar
  60. Shapiro JW, Williams ESCP, Turner PE (2016) Evolution of parasitism and mutualism between filamentous phage M13 and Escherichia coli. PeerJ 4:e2060. Scholar
  61. Sinsheimer RL (1966) φX: Multum in Parvo. In: Cairns J, Stent GS, Watson JD (eds) Phage and the origins of molecular biology. Cold Spring Harbor Laboratory, New York, pp 258–264Google Scholar
  62. Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69:531–569. Scholar
  63. Spruijt RB, Wolfs CJAM, Hemminga MA (2004) Membrane assembly of M13 major coat protein: evidence for a structural adaptation in the hinge region and a tilted transmembrane domain. Biochemistry 43:13972–13980. Scholar
  64. Stopar D, Spruijt RB, Wolfs CJ, Hemminga MA (1998) Mimicking initial interactions of bacteriophage M13 coat protein disassembly in model membrane systems. Biochemistry 37:10181–10187. Scholar
  65. Stopar D, Spruijt RB, Hemminga MA (2006a) Anchoring mechanisms of membrane-associated M13 major coat protein. Chem Phys Lipids 141:83–93. Scholar
  66. Stopar D, Strancar J, Spruijt RB, Hemminga MA (2006b) Motional restrictions of membrane proteins: a site-directed spin labeling study. Biophys J 91:3341–3348. Scholar
  67. Stopar D, Koehorst RBM, Spruijt RB, Hemminga MA (2009) Asymmetric dipping of bacteriophage M13 coat protein with increasing lipid bilayer thickness. Biochim Biophys Acta Biomembr 1788:2217–2221. Scholar
  68. Straus SK, Scott WRP, Symmons MF, Marvin DA (2008) On the structures of filamentous bacteriophage Ff (fd, f1, M13). Eur Biophys J 37:521. Scholar
  69. Straus SK, Scott WRP, Schwieters CD, Marvin DA (2011) Consensus structure of Pf1 filamentous bacteriophage from X-ray fibre diffraction and solid-state NMR. Eur Biophys J 40:221–234. Scholar
  70. Thiriot DS, Nevzorov AA, Zagyanskiy L et al (2004) Structure of the coat protein in Pf1 Bacteriophage determined by solid-state NMR spectroscopy. J Mol Biol 341:869–879. Scholar
  71. Thiriot DS, Nevzorov AA, Opella SJ (2005) Structural basis of the temperature transition of Pf1 bacteriophage. Protein Sci 14:1064–1070. Scholar
  72. Van Dalen A, De Kruijff B (2004) The role of lipids in membrane insertion and translocation of bacterial proteins. Biochim Biophys Acta, Mol Cell Res 1694:97–109. Scholar
  73. van de Ven FJ, van Os JW, Aelen JM et al (1993) Assignment of 1H, 15N, and backbone 13C resonances in detergent-solubilized M13 coat protein via multinuclear multidimensional NMR: a model for the coat protein monomer. Biochemistry 32:8322–8328CrossRefGoogle Scholar
  74. Vos WL, Nazarov PV, Koehorst RBM et al (2009) From “I” to “L” and back again: the odyssey of membrane-bound M13 protein. Trends Biochem Sci 34:249–255. Scholar
  75. Webster RE (1991) The tol gene products and the import of macromolecules into Escherichia Coli. Mol Microbiol 5:1005–1011CrossRefGoogle Scholar
  76. Webster RE (2001) Filamentous phage biology. In: Barbas CF III, Burton DR, Scott JK, Silverman GJ (eds) Phage display : a laboratory manual. Cold Spring Harbor Laboratory Press, New York, pp 1.1–1.37Google Scholar
  77. Welsh LC, Symmons MF, Marvin DA (2000) The molecular structure and structural transition of the α-helical capsid in filamentous bacteriophage Pf1. Acta Crystallogr Sect D Biol Crystallogr 56:137–150. Scholar
  78. Williams KA, Farrow NA, Deber CM, Kay LE (1996) Structure and dynamics of bacteriophage IKe major coat protein in MPG micelles by solution NMR. Biochemistry 35:5145–5157. Scholar
  79. Zeri AC, Mesleh MF, Nevzorov AA, Opella SJ (2003) Structure of the coat protein in fd filamentous bacteriophage particles determined by solid-state NMR spectroscopy. Proc Natl Acad Sci U S A 100:6458–6463. Scholar
  80. Zinder ND (1986) Single-stranded DNA-containing bacteriophages. BioEssays 5:84–87. Scholar
  81. Zinder ND, Valentine RC, Roger M, Stoeckenius W (1963) f1, a rod-shaped male-specific bacteriophage that contains DNA. Virology 20:638–640. Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of British ColumbiaVancouverCanada

Personalised recommendations