C-terminal domain of influenza virus polymerase PB2 subunit

[sharon sanders]

Published online: 25 February 2007; | doi:10.1038/nsmb1212
Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit


Franck Tarendeau<SUP>1, </SUP><SUP>5</SUP>, Julien Boudet<SUP>2, </SUP><SUP>5</SUP>, Delphine Guilligay<SUP>1</SUP>, Philippe J Mas<SUP>1</SUP>, Catherine M Bougault<SUP>2</SUP>, S?bastien Boulo<SUP>3</SUP>, Florence Baudin<SUP>3</SUP>, Rob W H Ruigrok<SUP>3</SUP>, Nathalie Daigle<SUP>4</SUP>, Jan Ellenberg<SUP>4</SUP>, Stephen Cusack<SUP>1</SUP>, Jean-Pierre Simorre<SUP>2</SUP> & Darren J Hart<SUP>1</SUP> <SUP>1</SUP> European Molecular Biology Laboratory (EMBL) Grenoble Outstation, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France.
<SUP>2</SUP> Institut de Biologie Structurale Jean-Pierre Ebel UMR 5075 CNRS-CEA-UJF, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
<SUP>3</SUP> Unit of Virus Host Cell Interactions UMR 5233 UJF-EMBL-CNRS, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France.
<SUP>4</SUP> EMBL Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
<SUP>5</SUP> These authors contributed equally to this work.
Correspondence should be addressed to Darren J Hart hart@embl.fr or Stephen Cusack cusack@embl.fr

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The trimeric influenza virus polymerase, comprising subunits PA, PB1 and PB2, is responsible for transcription and replication of the segmented viral RNA genome. Using a novel library-based screening technique called expression of soluble proteins by random incremental truncation (ESPRIT), we identified an independently folded C-terminal domain from PB2 and determined its solution structure by NMR. Using green fluorescent protein fusions, we show that both the domain and the full-length PB2 subunit are efficiently imported into the nucleus dependent on a previously overlooked bipartite nuclear localization sequence (NLS). The crystal structure of the domain complexed with human importin

5 shows how the last 20 residues unfold to permit binding to the import factor. The domain contains three surface residues implicated in adaptation from avian to mammalian hosts. One of these tethers the NLS-containing peptide to the core of the domain in the unbound state.

Not Open Access
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[sharon sanders]

Re: C-terminal domain of influenza virus polymerase PB2 subunit

Polymerase make copies of the viral genome and controls the production of viral proteins.

The polymerase molecule gives a signal when it wants to insert itself into a host nucleus.

This signal is "obeyed" by a transporter protein in the human host, importin alpha, which effectively conveys the polymerase into the host nucleus where it can proceed with the business of replicating viral genome.

Mutations/recombinations/reassortments of polymerase could change the efficiency of nuclear transport which would affect the ability of the virus to replicate.

Interfering with polymerase function could provide new ways to treat or prevent flu.