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J. Biol. Chem., Vol. 276, Issue 34, 31642-31650, August 24, 2001
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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.
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