1887

Abstract

The fusion (F) protein of measles virus performs refolding from the thermodynamically metastable prefusion form to the highly stable postfusion form via an activated unstable intermediate stage, to induce membrane fusion. Some amino acids involved in the fusion regulation cluster in the heptad repeat B (HR-B) domain of the stalk region, among which substitution of residue 465 by various amino acids revealed that fusion activity correlates well with its side chain length from the Cα (<0.01) and van der Waals volume (<0.001), except for Phe, Tyr, Trp, Pro and His carrying ring structures. Directed towards the head region, longer side chains of the non-ring-type 465 residues penetrate more deeply into the head region and may disturb the hydrophobic interaction between the stalk and head regions and cause destabilization of the molecule by lowering the energy barrier for refolding, which conferred the F protein enhanced fusion activity. Contrarily, the side chain of ring-type 465 residues turned away from the head region, resulting in not only no contact with the head region but also extensive coverage of the HR-B surface, which may prevent the dissociation of the HR-B bundle for initiation of membrane fusion and suppress fusion activity. Located in the HR-B domain just at the junction between the head and stalk regions, amino acid 465 is endowed with a possible ability to either destabilize or stabilize the F protein depending on its molecular volume and the direction of the side chain, regulating fusion activity of measles virus F protein.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000670
2017-02-01
2024-12-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/2/143.html?itemId=/content/journal/jgv/10.1099/jgv.0.000670&mimeType=html&fmt=ahah

References

  1. Choppin PW. Membrane proteins and virus virulence. Trans Am Clin Climatol Assoc 1984; 95:138–156[PubMed]
    [Google Scholar]
  2. Griffin DE. Measles virus. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA et al. (editors) Fields Virology, 6th ed. vol. 1 Philadelphia, PA: Lippincott Williams & Wilkins; 2013 pp. 1042–1069
    [Google Scholar]
  3. Bolt G, Pedersen IR. The role of subtilisin-like proprotein convertases for cleavage of the measles virus fusion glycoprotein in different cell types. Virology 1998; 252:387–398 [View Article][PubMed]
    [Google Scholar]
  4. Russell CJ, Kantor KL, Jardetzky TS, Lamb RA. A dual-functional paramyxovirus F protein regulatory switch segment: activation and membrane fusion. J Cell Biol 2003; 163:363–374 [View Article][PubMed]
    [Google Scholar]
  5. Plemper RK, Brindley MA, Iorio RM. Structural and mechanistic studies of measles virus illuminate paramyxovirus entry. PLoS Pathog 2011; 7:e1002058 [View Article][PubMed]
    [Google Scholar]
  6. Hashiguchi T, Ose T, Kubota M, Maita N, Kamishikiryo J et al. Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM. Nat Struct Mol Biol 2011; 18:135–141 [View Article][PubMed]
    [Google Scholar]
  7. Apte-Sengupta S, Negi S, Leonard VH, Oezguen N, Navaratnarajah CK et al. Base of the measles virus fusion trimer head receives the signal that triggers membrane fusion. J Biol Chem 2012; 287:33026–33035 [View Article][PubMed]
    [Google Scholar]
  8. Brindley MA, Takeda M, Plattet P, Plemper RK. Triggering the measles virus membrane fusion machinery. Proc Natl Acad Sci USA 2012; 109:E3018E3027 [View Article][PubMed]
    [Google Scholar]
  9. Navaratnarajah CK, Negi S, Braun W, Cattaneo R. Membrane fusion triggering: three modules with different structure and function in the upper half of the measles virus attachment protein stalk. J Biol Chem 2012; 287:38543–38551 [View Article][PubMed]
    [Google Scholar]
  10. Ader N, Brindley M, Avila M, Örvell C, Horvat B et al. Mechanism for active membrane fusion triggering by morbillivirus attachment protein. J Virol 2013; 87:314–326 [View Article][PubMed]
    [Google Scholar]
  11. Yin HS, Paterson RG, Wen X, Lamb RA, Jardetzky TS. Structure of the uncleaved ectodomain of the paramyxovirus (hPIV3) fusion protein. Proc Natl Acad Sci USA 2005; 102:9288–9293 [View Article][PubMed]
    [Google Scholar]
  12. Yin HS, Wen X, Paterson RG, Lamb RA, Jardetzky TS. Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation. Nature 2006; 439:38–44 [View Article][PubMed]
    [Google Scholar]
  13. Bose S, Heath CM, Shah PA, Alayyoubi M, Jardetzky TS et al. Mutations in the parainfluenza virus 5 fusion protein reveal domains important for fusion triggering and metastability. J Virol 2013; 87:13520–13531 [View Article][PubMed]
    [Google Scholar]
  14. Jardetzky TS, Lamb RA. Activation of paramyxovirus membrane fusion and virus entry. Curr Opin Virol 2014; 5:24–33 [View Article][PubMed]
    [Google Scholar]
  15. Bose S, Song AS, Jardetzky TS, Lamb RA. Fusion activation through attachment protein stalk domains indicates a conserved core mechanism of paramyxovirus entry into cells. J Virol 2014; 88:3925–3941 [View Article][PubMed]
    [Google Scholar]
  16. Wild TF, Fayolle J, Beauverger P, Buckland R. Measles virus fusion: role of the cysteine-rich region of the fusion glycoprotein. J Virol 1994; 68:7546–7548[PubMed]
    [Google Scholar]
  17. Plemper RK, Lakdawala AS, Gernert KM, Snyder JP, Compans RW. Structural features of paramyxovirus F protein required for fusion initiation. Biochemistry 2003; 42:6645–6655 [View Article][PubMed]
    [Google Scholar]
  18. Plemper RK, Compans RW. Mutations in the putative HR-C region of the measles virus F2 glycoprotein modulate syncytium formation. J Virol 2003; 77:4181–4190 [View Article][PubMed]
    [Google Scholar]
  19. Plemper RK, Erlandson KJ, Lakdawala AS, Sun A, Prussia A et al. A target site for template-based design of measles virus entry inhibitors. Proc Natl Acad Sci USA 2004; 101:5628–5633 [View Article][PubMed]
    [Google Scholar]
  20. Doyle J, Prussia A, White LK, Sun A, Liotta DC et al. Two domains that control prefusion stability and transport competence of the measles virus fusion protein. J Virol 2006; 80:1524–1536 [View Article][PubMed]
    [Google Scholar]
  21. Prussia AJ, Plemper RK, Snyder JP. Measles virus entry inhibitors: a structural proposal for mechanism of action and the development of resistance. Biochem 2008; 47:13573–13583 [CrossRef]
    [Google Scholar]
  22. Okada H, Itoh M, Nagata K, Takeuchi K. Previously unrecognized amino acid substitutions in the hemagglutinin and fusion proteins of measles virus modulate cell-cell fusion, hemadsorption, virus growth, and penetration rate. J Virol 2009; 83:8713–8721 [View Article][PubMed]
    [Google Scholar]
  23. Watanabe S, Shirogane Y, Suzuki SO, Ikegame S, Koga R et al. Mutant fusion proteins with enhanced fusion activity promote measles virus spread in human neuronal cells and brains of suckling hamsters. J Virol 2013; 87:2648–2659 [View Article][PubMed]
    [Google Scholar]
  24. Ayata M, Takeuchi K, Takeda M, Ohgimoto S, Kato S et al. The F gene of the Osaka-2 strain of measles virus derived from a case of subacute sclerosing panencephalitis is a major determinant of neurovirulence. J Virol 2010; 84:11189–11199 [View Article][PubMed]
    [Google Scholar]
  25. Okuno Y, Nakao T, Ishida N, Konno T, Mizutani H et al. Incidence of subacute sclerosing panencephalitis following measles and measles vaccination in Japan. Int J Epidemiol 1989; 18:684–689 [View Article][PubMed]
    [Google Scholar]
  26. Bellini WJ, Rota JS, Lowe LE, Katz RS, Dyken PR et al. Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis 2005; 192:1686–1693 [View Article][PubMed]
    [Google Scholar]
  27. Ayata M, Tanaka M, Kameoka K, Kuwamura M, Takeuchi K et al. Amino acid substitutions in the heptad repeat A and C regions of the F protein responsible for neurovirulence of measles virus Osaka-1 strain from a patient with subacute sclerosing panencephalitis. Virology 2016; 487:141–149 [View Article][PubMed]
    [Google Scholar]
  28. Satoh Y, Hirose M, Shogaki H, Wakimoto H, Kitagawa Y et al. Intramolecular complementation of measles virus fusion protein stability confers cell-cell fusion activity at 37 °C. FEBS Lett 2015; 589:152–158 [View Article][PubMed]
    [Google Scholar]
  29. Blaber M, Zhang XJ, Lindstrom JD, Pepiot SD, Baase WA et al. Determination of alpha-helix propensity within the context of a folded protein: sites 44 and 131 in bacteriophage T4 lysozyme. J Mol Biol 1994; 235:600–624 [View Article][PubMed]
    [Google Scholar]
  30. Zokarkar A, Connolly SA, Jardetzky TS, Lamb RA. Reversible inhibition of fusion activity of a paramyxovirus fusion protein by an engineered disulfide bond in the membrane-proximal external region. J Virol 2012; 86:12397–12401 [View Article][PubMed]
    [Google Scholar]
  31. Hutchens JO. Heat capacities, absolute entropies, and entropies of formation of amino acids and related compounds. In Sober HA. (editor) Handbook of Biochemistry, 2nd ed. Cleveland, Ohio: Chemical Rubber Co.; 1970 pp B60–B61
    [Google Scholar]
  32. Pickett SD, Sternberg MJ. Empirical scale of side-chain conformational entropy in protein folding. J Mol Biol 1993; 231:825–839 [View Article][PubMed]
    [Google Scholar]
  33. Abagyan R, Totrov M. Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins. J Mol Biol 1994; 235:983–1002 [View Article][PubMed]
    [Google Scholar]
  34. Najmanovich R, Kuttner J, Sobolev V, Edelman M. Sidechain flexibility in proteins upon ligand binding. Proteins 2000; 39:261–268 [View Article][PubMed]
    [Google Scholar]
  35. Ono N, Tatsuo H, Hidaka Y, Aoki T, Minagawa H et al. Measles viruses on throat swabs from measles patients use signaling lymphocytic activation molecule (CDw150) but not CD46 as a cellular receptor. J Virol 2001; 75:4399–4401 [View Article][PubMed]
    [Google Scholar]
  36. Ito N, Takayama-Ito M, Yamada K, Hosokawa J, Sugiyama M et al. Improved recovery of rabies virus from cloned cDNA using a vaccinia virus-free reverse genetics system. Microbiol Immunol 2003; 47:613–617 [View Article][PubMed]
    [Google Scholar]
  37. Fuerst TR, Niles EG, Studier FW, Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci USA 1986; 83:8122–8126 [View Article][PubMed]
    [Google Scholar]
  38. Wakimoto H, Shimodo M, Satoh Y, Kitagawa Y, Takeuchi K et al. F-actin modulates measles virus cell-cell fusion and assembly by altering the interaction between the matrix protein and the cytoplasmic tail of hemagglutinin. J Virol 2013; 87:1974–1984 [View Article][PubMed]
    [Google Scholar]
  39. Takeda M, Takeuchi K, Miyajima N, Kobune F, Ami Y et al. Recovery of pathogenic measles virus from cloned cDNA. J Virol 2000; 74:6643–6647 [View Article][PubMed]
    [Google Scholar]
  40. Plattet P, Langedijk JP, Zipperle L, Vandevelde M, Orvell C et al. Conserved leucine residue in the head region of morbillivirus fusion protein regulates the large conformational change during fusion activity. Biochemistry 2009; 48:9112–9121 [View Article][PubMed]
    [Google Scholar]
  41. Sheshberadaran H, Norrby E, Mccullough KC, Carpenter WC, Orvell C. The antigenic relationship between measles, canine distemper and rinderpest viruses studied with monoclonal antibodies. J Gen Virol 1986; 67:1381–1392 [View Article][PubMed]
    [Google Scholar]
  42. Lüthy R, Bowie JU, Eisenberg D. Assessment of protein models with three-dimensional profiles. Nature 1992; 356:83–85 [View Article][PubMed]
    [Google Scholar]
  43. Kawashima S, Pokarowski P, Pokarowska M, Kolinski A, Katayama T et al. AAindex: amino acid index database, progress report 2008. Nucleic Acids Res 2008; 36:D202–D205 [View Article][PubMed]
    [Google Scholar]
  44. Huang F, Nau WM. A conformational flexibility scale for amino acids in peptides. Angewandte Chemie 2003; 115:2371–2374 [CrossRef]
    [Google Scholar]
  45. Bowie JU, Lüthy R, Eisenberg D. A method to identify protein sequences that fold into a known three-dimensional structure. Science 1991; 253:164–170 [View Article][PubMed]
    [Google Scholar]
/content/journal/jgv/10.1099/jgv.0.000670
Loading
/content/journal/jgv/10.1099/jgv.0.000670
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error