Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2).
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.
Akarsu
Hatice
H
EMBL Grenoble Outstation, BP 181, 38042 Grenoble cedex 9, France.
Burmeister
Wilhelm P
WP
Petosa
Carlo
C
Petit
Isabelle
I
Müller
Christoph W
CW
Ruigrok
Rob W H
RW
Baudin
Florence
F
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods; D000070819:Discoidin Domain Receptor 1; D020558:GTP Phosphohydrolases / Q000378:metabolism; D009980:Influenza A virus / Q000737:chemistry / Q000378:metabolism*; D009981:Influenza B virus / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D020794:Receptor Protein-Tyrosine Kinases; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism
D008565:Membrane Proteins; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C083249:Ddr1 protein, mouse; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D020558:GTP Phosphohydrolases; D020931:ran GTP-Binding Protein