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The active sites of the influenza cap‐dependent endonuclease are on different polymerase subunits

The active sites of the influenza cap‐dependent endonuclease are on different polymerase subunits The cap‐dependent endonuclease of the influenza viral RNA polymerase, which produces the capped RNA primers that initiate viral mRNA synthesis, is comprised of two active sites, one for cap binding and one for endonuclease cleavage.We identify the amino acid sequences that constitute these two active sites and demonstrate that they are located on different polymerase subunits. Binding of the 5′ terminal sequence of virion RNA (vRNA) to the polymerase activates a tryptophan‐rich, cap‐binding sequence on the PB2 subunit. At least one of the tryptophans functions in cap binding, indicating that this active site is probably similar to that of other known cap‐binding proteins. Endonuclease cleavage, which is activated by the subsequent binding of the 3′ terminal sequence of vRNA, resides in a PB1 sequence that contains three essential acidic amino acids, similar to the active sites of other enzymes that cut polynucleotides to produce 3′‐OH ends. These results, coupled with those of our previous study, provide a molecular map of the five known essential active sites of the influenza viral polymerase. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

The active sites of the influenza cap‐dependent endonuclease are on different polymerase subunits

The EMBO Journal , Volume 20 (8) – May 17, 2002

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References (62)

Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/20.8.2078
pmid
11296240
Publisher site
See Article on Publisher Site

Abstract

The cap‐dependent endonuclease of the influenza viral RNA polymerase, which produces the capped RNA primers that initiate viral mRNA synthesis, is comprised of two active sites, one for cap binding and one for endonuclease cleavage.We identify the amino acid sequences that constitute these two active sites and demonstrate that they are located on different polymerase subunits. Binding of the 5′ terminal sequence of virion RNA (vRNA) to the polymerase activates a tryptophan‐rich, cap‐binding sequence on the PB2 subunit. At least one of the tryptophans functions in cap binding, indicating that this active site is probably similar to that of other known cap‐binding proteins. Endonuclease cleavage, which is activated by the subsequent binding of the 3′ terminal sequence of vRNA, resides in a PB1 sequence that contains three essential acidic amino acids, similar to the active sites of other enzymes that cut polynucleotides to produce 3′‐OH ends. These results, coupled with those of our previous study, provide a molecular map of the five known essential active sites of the influenza viral polymerase.

Journal

The EMBO JournalWiley

Published: May 17, 2002

Keywords: ; ; ;

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