New insights into structural disorder in human respiratory syncytial virus phosphoprotein and implications for binding of protein partners

Journal of Biological Chemistry

Volumn 292, Issue 6, 2017, Pages 2120-2131

  Pereira, Nelson ^a   Cardone, Christophe ^a   Lassoued, Safa ^a   Galloux, Marie ^b   Fix, Jenna ^b   Assrir, Nadine ^a   Lescop, Ewen ^a   Bontems, François ^a   Eléouët, Jean François ^b   Sizun, Christina ^a  

^a UNIVERSITÉ PARIS SACLAY   (France)

^b INRA Institut National de la Recherche Agronomique   (France)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEIC ACIDS; PROTEINS; VIRUSES;

DYNAMIC HETEROGENEITY; INTRINSICALLY DISORDERED REGIONS; LONG RANGE CONTACTS; MULTIPLE INTERACTIONS; PROTEIN-BINDING SITES; RESPIRATORY SYNCYTIAL VIRUS; SEQUENCE CONSERVATION; STRUCTURAL DISORDERS;

BINDING SITES;

VIRUS PHOSPHOPROTEIN; INTRINSICALLY DISORDERED PROTEIN; PHOSPHOPROTEIN; PROTEIN BINDING;

AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; HUMAN RESPIRATORY SYNCYTIAL VIRUS; MOLECULAR DYNAMICS; NONHUMAN; OLIGOMERIZATION; PROTEIN BINDING; PROTEIN DETERMINATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN STRUCTURE; STRUCTURE ANALYSIS; VIRUS IDENTIFICATION; AMINO ACID SEQUENCE; CHEMISTRY; ELECTRON SPIN RESONANCE; METABOLISM; NUCLEAR MAGNETIC RESONANCE; PROTEIN SECONDARY STRUCTURE; SEQUENCE HOMOLOGY;

AMINO ACID SEQUENCE; ELECTRON SPIN RESONANCE SPECTROSCOPY; INTRINSICALLY DISORDERED PROTEINS; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PHOSPHOPROTEINS; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; RESPIRATORY SYNCYTIAL VIRUS, HUMAN; SEQUENCE HOMOLOGY, AMINO ACID;

EID: 85012065390     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M116.765958     Document Type: Article

References (58)

1. Afonso, C. L., Amarasinghe, G. K., Banyai, K., Bao, Y., Basler, C. F., Bavari, S., Bejerman, N., Blasdell, K. R., Briand, F. X., Briese, T., Bukreyev, A., Calisher, C. H., Chandran, K., Cheng, J., Clawson, A. N., et al. (2016) Taxonomy of the order mononegavirales: update 2016. Arch. Virol. 161, 2351-2360
2. Collins, P. L., and Melero, J. A. (2011) Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years. Virus Res. 162, 80-99
3. Nair, H., Nokes, D. J., Gessner, B. D., Dherani, M., Madhi, S. A., Singleton, R. J., O'Brien, K. L., Roca, A., Wright, P. F., Bruce, N., Chandran, A., Theodoratou, E., Sutanto, A., Sedyaningsih, E. R., Ngama, M., et al. (2010) Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375, 1545-1555
4. Mazur, N. I., Martinón-Torres, F., Baraldi, E., Fauroux, B., Greenough, A., Heikkinen, T., Manzoni, P., Mejias, A., Nair, H., Papadopoulos, N. G., Polack, F. P., Ramilo, O., Sharland, M., Stein, R., Madhi, S. A., Bont, L., and Respiratory Syncytial Virus Network (ReSViNET) (2015) Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics. Lancet Respir. Med. 3, 888-900
5. Collins, P. L., and Karron, R. A. (2013) Respiratory Syncytial Virus and Metapneumovirus. in Fields Virology (Knipe, D. M., and Howley, P. M., eds) 6th Ed., pp. 1086-1123, Lippinscot Williams & Wilkins, Wolters Kluwer, Philadelphia, PA
6. Cox, R., and Plemper, R. K. (2016) Structure-guided design of small-molecule therapeutics against RSV disease. Expert Opin. Drug Discov. 11, 543-556
7. Cox, R., and Plemper, R. K. (2015) The paramyxovirus polymerase complex as a target for next-generation anti-paramyxovirus therapeutics. Front. Microbiol. 6, 459
8. García, J., García-Barreno, B., Vivo, A., and Melero, J. A. (1993) Cytoplasmic inclusions of respiratory syncytial virus-infected cells: formation of inclusion bodies in transfected cells that coexpress the nucleoprotein, the phosphoprotein, and the 22K protein. Virology 195, 243-247
9. Lahaye, X., Vidy, A., Pomier, C., Obiang, L., Harper, F., Gaudin, Y., and Blondel, D. (2009) Functional characterization of Negri bodies (NBs) in rabies virus-infected cells: evidence that NBs are sites of viral transcription and replication. J. Virol. 83, 7948-7958
10. Heinrich, B. S., Cureton, D. K., Rahmeh, A. A., and Whelan, S. P. (2010) Protein expression redirects vesicular stomatitis virus RNA synthesis to cytoplasmic inclusions. PLoS Pathog. 6, e1000958
11. Grosfeld, H., Hill, M. G., and Collins, P. L. (1995) RNA replication by respiratory syncytial virus (RSV) is directed by the N, P, and L proteins; transcription also occurs under these conditions but requires RSV superinfection for efficient synthesis of full-length mRNA. J. Virol. 69, 5677-5686
12. Yu, Q., Hardy, R. W., and Wertz, G. W. (1995) Functional cDNA clones of the human respiratory syncytial (RS) virus N, P, and L proteins support replication of RS virus genomic RNA analogs and define minimal transacting requirements for RNA replication. J. Virol. 69, 2412-2419
13. Tran, T. L., Castagné, N., Bhella, D., Varela, P. F., Bernard, J., Chilmonczyk, S., Berkenkamp, S., Benhamo, V., Grznarova, K., Grosclaude, J., Nespoulos, C., Rey, F. A., and Eléouët, J. F. (2007) The nine C-terminal amino acids of the respiratory syncytial virus protein P are necessary and sufficient for binding to ribonucleoprotein complexes in which six ribonucleotides are contacted per N protein protomer. J. Gen. Virol. 88, 196-206
14. Galloux, M., Tarus, B., Blazevic, I., Fix, J., Duquerroy, S., and Eléouët, J. F. (2012) Characterization of a viral phosphoprotein binding site on the surface of the respiratory syncytial nucleoprotein. J. Virol. 86, 8375-8387
15. García-Barreno, B., Delgado, T., and Melero, J. A. (1996) Identification of protein regions involved in the interaction of human respiratory syncytial virus phosphoprotein and nucleoprotein: significance for nucleocapsid assembly and formation of cytoplasmic inclusions. J. Virol. 70, 801-808
16. Slack, M. S., and Easton, A. J. (1998) Characterization of the interaction of the human respiratory syncytial virus phosphoprotein and nucleocapsid protein using the two-hybrid system. Virus Res. 55, 167-176
17. Mason, S. W., Aberg, E., Lawetz, C., DeLong, R., Whitehead, P., and Liuzzi, M. (2003) Interaction between human respiratory syncytial virus (RSV) M2-1 and P proteins is required for reconstitution of M2-1-dependent RSV minigenome activity. J. Virol. 77, 10670-10676
18. Blondot, M. L., Dubosclard, V., Fix, J., Lassoued, S., Aumont-Nicaise, M., Bontems, F., Eléouët, J. F., and Sizun, C. (2012) Structure and functional analysis of the RNA- and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein. PLoS Pathog. 8, e1002734
19. Tran, T. L., Castagné, N., Dubosclard, V., Noinville, S., Koch, E., Moudjou, M., Henry, C., Bernard, J., Yeo, R. P., and Eléouët, J. F. (2009) The respiratory syncytial virus M2-1 protein forms tetramers and interacts with RNA and P in a competitive manner. J. Virol. 83, 6363-6374
20. Villanueva, N., Hardy, R., Asenjo, A., Yu, Q., and Wertz, G. (2000) The bulk of the phosphorylation of human respiratory syncytial virus phosphoprotein is not essential but modulates viral RNA transcription and replication. J. Gen. Virol. 81, 129-133
21. Asenjo, A., Calvo, E., and Villanueva, N. (2006) Phosphorylation of human respiratory syncytial virus P protein at threonine 108 controls its interaction with the M2-1 protein in the viral RNA polymerase complex. J. Gen. Virol. 87, 3637-3642
22. Asenjo, A., and Villanueva, N. (2016) Phosphorylation of the human respiratory syncytial virus P protein mediates M2-2 regulation of viral RNA synthesis, a process that involves two P proteins. Virus Res. 211, 117-125
23. Curran, J., Marq, J. B., and Kolakofsky, D. (1995) An N-terminal domain of the Sendai paramyxovirus P protein acts as a chaperone for the NP protein during the nascent chain assembly step of genome replication. J. Virol. 69, 849-855
24. Galloux, M., Gabiane, G., Sourimant, J., Richard, C. A., England, P., Moudjou, M., Aumont-Nicaise, M., Fix, J., Rameix-Welti, M. A., and Eléouët, J. F. (2015) Identification and characterization of the binding site of the respiratory syncytial virus phosphoprotein to RNA-free nucleoprotein. J. Virol. 89, 3484-3496
25. Castagné, N., Barbier, A., Bernard, J., Rezaei, H., Huet, J. C., Henry, C., Da Costa, B., and Eléouët, J. F. (2004) Biochemical characterization of the respiratory syncytial virus P-P and P-N protein complexes and localization of the P protein oligomerization domain. J. Gen. Virol. 85, 1643-1653
26. Simabuco, F. M., Asara, J. M., Guerrero, M. C., Libermann, T. A., Zerbini, L. F., and Ventura, A. M. (2011) Structural analysis of human respiratory syncytial virus p protein: identification of intrinsically disordered domains. Braz. J. Microbiol. 42, 340-345
27. Noval, M. G., Esperante, S. A., Molina, I. G., Chemes, L. B., and Prat-Gay, G. (2016) Intrinsic disorder to order transitions in the scaffold phosphoprotein P from the respiratory syncytial virus RNA polymerase complex. Biochemistry 55, 1441-1454
28. Llorente, M. T., Taylor, I. A., López-Viñas, E., Gomez-Puertas, P., Calder, L. J., García-Barreno, B., and Melero, J. A. (2008) Structural properties of the human respiratory syncytial virus P protein: evidence for an elongated homotetrameric molecule that is the smallest orthologue within the family of paramyxovirus polymerase cofactors. Proteins 72, 946-958
29. Kosol, S., Contreras-Martos, S., Cedeño, C., and Tompa, P. (2013) Structural characterization of intrinsically disordered proteins by NMR spectroscopy. Molecules 18, 10802-10828
30. Sourimant, J., Rameix-Welti, M. A., Gaillard, A. L., Chevret, D., Galloux, M., Gault, E., and Eléouët, J. F. (2015) Fine mapping and characterization of the L-polymerase-binding domain of the respiratory syncytial virus phosphoprotein. J. Virol. 89, 4421-4433
31. Shen, Y., Delaglio, F., Cornilescu, G., and Bax, A. (2009) TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J. Biomol. NMR 44, 213-223
32. Camilloni, C., De Simone, A., Vranken, W. F., and Vendruscolo, M. (2012) Determination of secondary structure populations in disordered states of proteins using nuclear magnetic resonance chemical shifts. Biochemistry 51, 2224-2231
33. Clore, G. M., and Iwahara, J. (2009) Theory, practice, and applications of paramagnetic relaxation enhancement for the characterization of transient low-population states of biological macromolecules and their complexes. Chem. Rev. 109, 4108-4139
34. Lietzow, M. A., Jamin, M., Dyson, H. J., and Wright, P. E. (2002) Mapping long-range contacts in a highly unfolded protein. J. Mol. Biol. 322, 655-662
35. Gillespie, J. R., and Shortle, D. (1997) Characterization of long-range structure in the denatured state of staphylococcal nuclease: I. paramagnetic relaxation enhancement by nitroxide spin labels. J. Mol. Biol. 268, 158-169
36. Wright, P. E., and Dyson, H. J. (2009) Linking folding and binding. Curr. Opin. Struct. Biol. 19, 31-38
37. Mohan, A., Oldfield, C. J., Radivojac, P., Vacic, V., Cortese, M. S., Dunker, A. K., and Uversky, V. N. (2006) Analysis of molecular recognition features (MoRFs). J. Mol. Biol. 362, 1043-1059
38. Bakker, S. E., Duquerroy, S., Galloux, M., Loney, C., Conner, E., Eléouët, J. F., Rey, F. A., and Bhella, D. (2013) The respiratory syncytial virus nucleoprotein-RNA complex forms a left-handed helical nucleocapsid. J. Gen. Virol. 94, 1734-1738
39. Ouizougun-Oubari, M., Pereira, N., Tarus, B., Galloux, M., Lassoued, S., Fix, J., Tortorici, M. A., Hoos, S., Baron, B., England, P., Desmaele, D., Couvreur, P., Bontems, F., Rey, F. A., et al. (2015) A druggable pocket at the nucleocapsid/phosphoprotein interaction site of human respiratory syncytial virus. J. Virol. 89, 11129-11143
40. Renner, M., Bertinelli, M., Leyrat, C., Paesen, G. C., Saraiva de Oliveira, L. F., Huiskonen, J. T., and Grimes, J. M. (2016) Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein. Elife 5, e12627
41. Llorente, M. T., García-Barreno, B., Calero, M., Camafeita, E., López, J. A., Longhi, S., Ferrón, F., Varela, P. F., and Melero, J. A. (2006) Structural analysis of the human respiratory syncytial virus phosphoprotein: characterization of an α-helical domain involved in oligomerization. J. Gen. Virol. 87, 159-169
42. Asenjo, A., Mendieta, J., Gómez-Puertas, P., and Villanueva, N. (2008) Residues in human respiratory syncytial virus P protein that are essential for its activity on RNA viral synthesis. Virus Res. 132, 160-173
43. Ruigrok, R. W., Crépin, T., and Kolakofsky, D. (2011) Nucleoproteins and nucleocapsids of negative-strand RNA viruses. Curr. Opin. Microbiol. 14, 504-510
44. Karlin, D., and Belshaw, R. (2012) Detecting remote sequence homology in disordered proteins: discovery of conserved motifs in the N-termini of Mononegavirales phosphoproteins. PLoS ONE 7, e31719
45. Leyrat, C., Renner, M., Harlos, K., and Grimes, J. M. (2013) Solution and crystallographic structures of the central region of the phosphoprotein from human metapneumovirus. PLoS ONE 8, e80371
46. Cox, R., Green, T. J., Purushotham, S., Deivanayagam, C., Bedwell, G. J., Prevelige, P. E., and Luo, M. (2013) Structural and functional characterization of the mumps virus phosphoprotein. J. Virol. 87, 7558-7568
47. Cox, R., Pickar, A., Qiu, S., Tsao, J., Rodenburg, C., Dokland, T., Elson, A., He, B., and Luo, M. (2014) Structural studies on the authentic mumps virus nucleocapsid showing uncoiling by the phosphoprotein. Proc. Natl. Acad. Sci. U.S.A. 111, 15208-15213
48. Munday, D. C., Wu, W., Smith, N., Fix, J., Noton, S. L., Galloux, M., Touzelet, O., Armstrong, S. D., Dawson, J. M., Aljabr, W., Easton, A. J., Rameix-Welti, M. A., de Oliveira, A. P., Simabuco, F. M., Ventura, A. M., et al. (2015) Interactome analysis of the human respiratory syncytial virus RNA polymerase complex identifies protein chaperones as important cofactors that promote L-protein stability and RNA synthesis. J. Virol. 89, 917-930
49. Khattar, S. K., Yunus, A. S., and Samal, S. K. (2001) Mapping the domains on the phosphoprotein of bovine respiratory syncytial virus required for N-P and P-L interactions using a minigenome system. J. Gen. Virol. 82, 775-779
50. Lu, B., Brazas, R., Ma, C. H., Kristoff, T., Cheng, X., and Jin, H. (2002) Identification of temperature-sensitive mutations in the phosphoprotein of respiratory syncytial virus that are likely involved in its interaction with the nucleoprotein. J. Virol. 76, 2871-2880
51. Shapiro, A. B., Gao, N., O'Connell, N., Hu, J., Thresher, J., Gu, R. F., Overman, R., Hardern, I. M., and Sproat, G. G. (2014) Quantitative investigation of the affinity of human respiratory syncytial virus phosphoprotein C-terminus binding to nucleocapsid protein. Virol. J. 11, 191
52. Vranken, W. F., Boucher, W., Stevens, T. J., Fogh, R. H., Pajon, A., Llinas, M., Ulrich, E. L., Markley, J. L., Ionides, J., and Laue, E. D. (2005) The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins 59, 687-696
53. Lescop, E., Schanda, P., and Brutscher, B. (2007) A set of BEST triple-resonance experiments for time-optimized protein resonance assignment. J. Magn. Reson. 187, 163-169
54. Sali, A., and Blundell, T. L. (1993) Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815
55. Guntert, P. (2004) Automated NMR structure calculation with CYANA. Methods Mol. Biol. 278, 353-378
56. Schrodinger, L. (2010) The AxPyMOL Molecular Graphics Plugin for Microsoft PowerPoint, version 1.0, Schrödinger, LLC, New York
57. Sievers, F., Wilm, A., Dineen, D., Gibson, T. J., Karplus, K., Li, W., Lopez, R., McWilliam, H., Remmert, M., Söding, J., Thompson, J. D., and Higgins, D. G. (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539
58. Gouet, P., Courcelle, E., Stuart, D. I., and Metoz, F. (1999) ESPript, analysis of multiple sequence alignments in PostScript. Bioinformatics 15, 305-308