title: Influenza A virus protein PB1-F2 from different strains shows distinct structural signatures.
abstract: The proapoptotic influenza A virus PB1-F2 protein contributes to viral pathogenicity and is present in most human and avian influenza isolates. The structures of full-length PB1-F2 of the influenza strains Pandemic flu 2009 H1N1, 1918 Spanish flu H1N1, Bird flu H5N1 and H1N1 PR8, have been characterized by NMR and CD spectroscopy. The study was conducted using chemically synthesized full-length PB1-F2 protein and fragments thereof. The amino acid residues 30-70 of PR8 PB1-F2 were found to be responsible for amyloid formation of the protein, which could be assigned to formation of β-sheet structures, although α-helices were the only structural features detected under conditions that mimic a membranous environment. At membranous conditions, in which the proteins are found in their most structured state, significant differences become apparent between the PB1-F2 variants investigated. In contrast to Pandemic flu 2009 H1N1 and PR8 PB1-F2, which exhibit a continuous extensive C-terminal α-helix, both Spanish flu H1N1 and Bird flu H5N1 PB1-F2 contain a loop region with residues 66-71 that divides the C-terminus into two shorter helices. The observed structural differences are located to the C-terminal ends of the proteins to which most of the known functions of these proteins have been assigned. A C-terminal helix-loop-helix motif might be a structural signature for PB1-F2 of the highly pathogenic influenza viruses as observed for 1918 Spanish flu H1N1 and Bird flu H5N1 PB1-F2. This signature could indicate the pathological nature of viruses emerging in the future and thus aid in the recognition of these viruses.
authors.affiliation: Department of Chemistry and Centre of Pharmacy, University of Bergen, N-5007 Bergen, Norway.
authors.forename: Sara M Ø
authors.initials: SM
authors.lastname: Solbak
authors.forename: Alok
authors.initials: A
authors.lastname: Sharma
authors.forename: Karsten
authors.initials: K
authors.lastname: Bruns
authors.forename: René
authors.initials: R
authors.lastname: Röder
authors.forename: David
authors.initials: D
authors.lastname: Mitzner
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hahn
authors.forename: Rebekka
authors.initials: R
authors.lastname: Niebert
authors.forename: Anni
authors.initials: A
authors.lastname: Vedeler
authors.forename: Petra
authors.initials: P
authors.lastname: Henklein
authors.forename: Peter
authors.initials: P
authors.lastname: Henklein
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schubert
authors.forename: Victor
authors.initials: V
authors.lastname: Wray
authors.forename: Torgils
authors.initials: T
authors.lastname: Fossen
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000235:genetics; D018257:Helix-Loop-Helix Motifs; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry* / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry* / Q000235:genetics; D013045:Species Specificity; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D000682:Amyloid; C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins