| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 34, 31642-31650, August 24, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Institut für Virologie, Tierärztliche
Hochschule Hannover, Bünteweg 17, D-30559 Hannover, Germany
The F (fusion) protein of the respiratory
syncytial viruses is synthesized as an inactive precursor
F0 that is proteolytically processed at the
multibasic sequence KKRKRR136 into the subunits
F1 and F2 by the cellular protease furin. This maturation process is essential for the F protein to gain fusion competence. We observed that proteolytic cleavage additionally occurs
at another basic motif, RARR109, that
also meets the requirements for furin recognition. Cleavage at both
sites leads to the removal from the polypeptide chain of a glycosylated
peptide of 27 amino acids. When the sequence RARR109 was
changed to NANR109 or to RANN109 by
site-directed mutagenesis, cleavage by furin was completely prevented.
Although the mutants were still processed at position Arg136, they did not show any syncytia formation.
Proteolytic cleavage of the modified motifs was achieved by treatment
of transfected cells with trypsin converting the F mutants into their
fusogenic forms. Our findings indicate that both furin consensus
sequences have to be cleaved in order to activate the fusion protein.
This publication is dedicated to Prof. Dr. R. Rott on the occasion of
his 75th birthday.
Proteolytic Activation of Respiratory Syncytial Virus Fusion
Protein
CLEAVAGE AT TWO FURIN CONSENSUS SEQUENCES*
*
The work was supported Deutsche Forschungsgemeinschaft Grant
HE 1168/11-1/2 (to G. H.) and European Community Grant
QLK2-CT-1999-00443.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Institut für
Virologie, Tierärztliche Hochschule Hannover, Bünteweg 17, D-30559 Hannover, Germany. Fax: 49-511-953-8898; E-mail:
Georg.Herrler@tiho- hannover.de.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Johnstone, S. Guil, M. A. Rico, B. Garcia-Barreno, D. Lopez, J. A. Melero, and M. Del Val Relevance of viral context and diversity of antigen-processing routes for respiratory syncytial virus cytotoxic T-lymphocyte epitopes J. Gen. Virol., September 1, 2008; 89(9): 2194 - 2203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shirogane, M. Takeda, M. Iwasaki, N. Ishiguro, H. Takeuchi, Y. Nakatsu, M. Tahara, H. Kikuta, and Y. Yanagi Efficient Multiplication of Human Metapneumovirus in Vero Cells Expressing the Transmembrane Serine Protease TMPRSS2 J. Virol., September 1, 2008; 82(17): 8942 - 8946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Herfst, V. Mas, L. S. Ver, R. J. Wierda, A. D. M. E. Osterhaus, R. A. M. Fouchier, and J. A. Melero Low-pH-Induced Membrane Fusion Mediated by Human Metapneumovirus F Protein Is a Rare, Strain-Dependent Phenomenon J. Virol., September 1, 2008; 82(17): 8891 - 8895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rawling, B. Garcia-Barreno, and J. A. Melero Insertion of the Two Cleavage Sites of the Respiratory Syncytial Virus Fusion Protein in Sendai Virus Fusion Protein Leads to Enhanced Cell-Cell Fusion and a Decreased Dependency on the HN Attachment Protein for Activity J. Virol., June 15, 2008; 82(12): 5986 - 5998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Eckardt-Michel, M. Lorek, D. Baxmann, T. Grunwald, G. M. Keil, and G. Zimmer The Fusion Protein of Respiratory Syncytial Virus Triggers p53-Dependent Apoptosis J. Virol., April 1, 2008; 82(7): 3236 - 3249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Winter, C. Schwegmann-Wessels, U. Neumann, and G. Herrler The Spike Protein of Infectious Bronchitis Virus Is Retained Intracellularly by a Tyrosine Motif J. Virol., March 15, 2008; 82(6): 2765 - 2771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Gardner and R. E. Dutch A Conserved Region in the F2 Subunit of Paramyxovirus Fusion Proteins Is Involved In Fusion Regulation J. Virol., August 1, 2007; 81(15): 8303 - 8314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. BROOR and P. BHARAJ Avian and Human Metapneumovirus Ann. N.Y. Acad. Sci., April 1, 2007; 1102(1): 66 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Crim, S. A. Audet, S. A. Feldman, H. S. Mostowski, and J. A. Beeler Identification of Linear Heparin-Binding Peptides Derived from Human Respiratory Syncytial Virus Fusion Glycoprotein That Inhibit Infectivity J. Virol., January 1, 2007; 81(1): 261 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Martin, L. J. Calder, B. Garcia-Barreno, J. J. Skehel, and J. A. Melero Sequence elements of the fusion peptide of human respiratory syncytial virus fusion protein required for activity J. Gen. Virol., June 1, 2006; 87(6): 1649 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-F. Valarcher, J. Furze, S. G. Wyld, R. Cook, G. Zimmer, G. Herrler, and G. Taylor Bovine respiratory syncytial virus lacking the virokinin or with a mutation in furin cleavage site RA(R/K)R109 induces less pulmonary inflammation without impeding the induction of protective immunity in calves J. Gen. Virol., June 1, 2006; 87(6): 1659 - 1667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Aspehaug, A. B. Mikalsen, M. Snow, E. Biering, and S. Villoing Characterization of the Infectious Salmon Anemia Virus Fusion Protein J. Virol., October 1, 2005; 79(19): 12544 - 12553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zimmer, S. Bossow, L. Kolesnikova, M. Hinz, W. J. Neubert, and G. Herrler A Chimeric Respiratory Syncytial Virus Fusion Protein Functionally Replaces the F and HN Glycoproteins in Recombinant Sendai Virus J. Virol., August 15, 2005; 79(16): 10467 - 10477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hanika, B. Larisch, E. Steinmann, C. Schwegmann-Wessels, G. Herrler, and G. Zimmer Use of influenza C virus glycoprotein HEF for generation of vesicular stomatitis virus pseudotypes J. Gen. Virol., May 1, 2005; 86(5): 1455 - 1465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Ruiz-Arguello, D. Martin, S. A. Wharton, L. J. Calder, S. R. Martin, O. Cano, M. Calero, B. Garcia-Barreno, J. J. Skehel, and J. A. Melero Thermostability of the human respiratory syncytial virus fusion protein before and after activation: implications for the membrane-fusion mechanism J. Gen. Virol., December 1, 2004; 85(12): 3677 - 3687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Biacchesi, M. H. Skiadopoulos, L. Yang, E. W. Lamirande, K. C. Tran, B. R. Murphy, P. L. Collins, and U. J. Buchholz Recombinant Human Metapneumovirus Lacking the Small Hydrophobic SH and/or Attachment G Glycoprotein: Deletion of G Yields a Promising Vaccine Candidate J. Virol., December 1, 2004; 78(23): 12877 - 12887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Johnstone, P. de Leon, F. Medina, J. A. Melero, B. Garcia-Barreno, and M. D. Val Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F glycoprotein of the Long strain of respiratory syncytial virus J. Gen. Virol., November 1, 2004; 85(11): 3229 - 3238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schwegmann-Wessels, M. Al-Falah, D. Escors, Z. Wang, G. Zimmer, H. Deng, L. Enjuanes, H. Y. Naim, and G. Herrler A Novel Sorting Signal for Intracellular Localization Is Present in the S Protein of a Porcine Coronavirus but Absent from Severe Acute Respiratory Syndrome-associated Coronavirus J. Biol. Chem., October 15, 2004; 279(42): 43661 - 43666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Konig, K. Giesow, K. Schuldt, U. J. Buchholz, and G. M. Keil A novel protein expression strategy using recombinant bovine respiratory syncytial virus (BRSV): modifications of the peptide sequence between the two furin cleavage sites of the BRSV fusion protein yield secreted proteins, but affect processing and function of the BRSV fusion protein J. Gen. Virol., July 1, 2004; 85(7): 1815 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Kohl, G. Zimmer, I. Greiser-Wilke, L. Haas, V. Moennig, and G. Herrler The surface glycoprotein E2 of bovine viral diarrhoea virus contains an intracellular localization signal J. Gen. Virol., May 1, 2004; 85(5): 1101 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Easton, J. B. Domachowske, and H. F. Rosenberg Animal Pneumoviruses: Molecular Genetics and Pathogenesis Clin. Microbiol. Rev., April 1, 2004; 17(2): 390 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zimmer, M. Rohn, G. P. McGregor, M. Schemann, K.-K. Conzelmann, and G. Herrler Virokinin, a Bioactive Peptide of the Tachykinin Family, Is Released from the Fusion Protein of Bovine Respiratory Syncytial Virus J. Biol. Chem., November 21, 2003; 278(47): 46854 - 46861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Douglas, M. L. Panis, E. Ho, K.-Y. Lin, S. H. Krawczyk, D. M. Grant, R. Cai, S. Swaminathan, and T. Cihlar Inhibition of Respiratory Syncytial Virus Fusion by the Small Molecule VP-14637 via Specific Interactions with F Protein J. Virol., May 1, 2003; 77(9): 5054 - 5064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Schlender, G. Zimmer, G. Herrler, and K.-K. Conzelmann Respiratory Syncytial Virus (RSV) Fusion Protein Subunit F2, Not Attachment Protein G, Determines the Specificity of RSV Infection J. Virol., April 15, 2003; 77(8): 4609 - 4616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. van Bleek, M. C. Poelen, R. van der Most, H. F. Brugghe, H. A. M. Timmermans, C. J. Boog, P. Hoogerhout, H. G. Otten, and C. A. C. M. van Els Identification of Immunodominant Epitopes Derived from the Respiratory Syncytial Virus Fusion Protein That Are Recognized by Human CD4 T Cells J. Virol., December 20, 2002; 77(2): 980 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zimmer, K.-K. Conzelmann, and G. Herrler Cleavage at the Furin Consensus Sequence RAR/KR109 and Presence of the Intervening Peptide of the Respiratory Syncytial Virus Fusion Protein Are Dispensable for Virus Replication in Cell Culture J. Virol., August 12, 2002; 76(18): 9218 - 9224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Smith, M. C. Lawrence, and P. M. Colman Modelling the structure of the fusion protein from human respiratory syncytial virus Protein Eng. Des. Sel., May 1, 2002; 15(5): 365 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. von Messling and R. Cattaneo Amino-Terminal Precursor Sequence Modulates Canine Distemper Virus Fusion Protein Function J. Virol., March 27, 2002; 76(9): 4172 - 4180. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
