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Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2).

ABSTRACT: During influenza virus infection, viral ribonucleoproteins (vRNPs) are replicated in the nucleus and must be exported to the cytoplasm before assembling into mature viral particles. Nuclear export is mediated by the cellular protein Crm1 and putatively by the viral protein NEP/NS2. Proteolytic cleavage of NEP defines an N-terminal domain which mediates RanGTP-dependent binding to Crm1 and a C-terminal domain which binds to the viral matrix protein M1. The 2.6 A crystal structure of the C-terminal domain reveals an amphipathic helical hairpin which dimerizes as a four-helix bundle. The NEP-M1 interaction involves two critical epitopes: an exposed tryptophan (Trp78) surrounded by a cluster of glutamate residues on NEP, and the basic nuclear localization signal (NLS) of M1. Implications for vRNP export are discussed.

SUBMITTER: Akarsu H

PROVIDER: S-EPMC212717 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2).

Akarsu Hatice H Burmeister Wilhelm P WP Petosa Carlo C Petit Isabelle I Müller Christoph W CW Ruigrok Rob W H RW Baudin Florence F

The EMBO journal 20030901 18

During influenza virus infection, viral ribonucleoproteins (vRNPs) are replicated in the nucleus and must be exported to the cytoplasm before assembling into mature viral particles. Nuclear export is mediated by the cellular protein Crm1 and putatively by the viral protein NEP/NS2. Proteolytic cleavage of NEP defines an N-terminal domain which mediates RanGTP-dependent binding to Crm1 and a C-terminal domain which binds to the viral matrix protein M1. The 2.6 A crystal structure of the C-termina ...[more]

PMID: 12970177

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