2HN8

Structural characterization and oligomerization of PB1-F2, a pro-apoptotic influenza A virus protein

Summary for 2HN8

• Entry DOI: 10.2210/pdb2hn8/pdb
• NMR Information: BMRB: 7258
• Descriptor: Protein PB1-F2 (1 entity in total)
• Functional Keywords: pro-apoptotic mitochondrial targeting protein, viral protein
• Cellular location: Host mitochondrion inner membrane: P0C0U1
• Total number of polymer chains: 1
• Total formula weight: 4848.93

Authors

Bruns, K.,Studtrucker, N.,Sharma, A.,Fossen, T.,Mitzner, D.,Eissmann, A.,Tessmer, U.,Roder, R.,Henklein, P.,Wray, V.,Schubert, U. (deposition date: 2006-07-12, release date: 2006-11-07, Last modification date: 2024-05-29)

Primary citation

Bruns, K.,Studtrucker, N.,Sharma, A.,Fossen, T.,Mitzner, D.,Eissmann, A.,Tessmer, U.,Roder, R.,Henklein, P.,Wray, V.,Schubert, U.
Structural characterization and oligomerization of PB1-F2, a pro-apoptotic influenza A virus protein.
J.Biol.Chem., 282:353-363, 2007

PubMed Abstract: Recently, a novel 87-amino acid influenza A virus protein with proapoptotic properties, PB1-F2, has been reported that originates from an alternative reading frame in the PB1 polymerase gene and is encoded in most known human influenza A virus isolates. Here we characterize the molecular structure of a biologically active synthetic version of the protein (sPB1-F2). Western blot analysis, chemical cross-linking, and NMR spectroscopy afforded direct evidence of the inherent tendency of sPB1-F2 to undergo oligomerization mediated by two distinct domains located in the N and C termini, respectively. CD and (1)H NMR spectroscopic analyses indicate that the stability of structured regions in the molecule clearly depends upon the hydrophobicity of the solvent. In aqueous solutions, the behavior of sPB1-F2 is typical of a largely random coil peptide that, however, adopts alpha-helical structure upon the addition of membrane mimetics. (1)H NMR analysis of three overlapping peptides afforded, for the first time, direct experimental evidence of the presence of a C-terminal region with strong alpha-helical propensity comprising amino acid residues Ile(55)-Lys(85) connected via an essentially random coil structure to a much weaker helix-like region, located in the N terminus between residues Trp(9) and Lys(20). The C-terminal helix is not a true amphipathic helix and is more compact than previously predicted. It corresponds to a positively charged region previously shown to include the mitochondrial targeting sequence of PB1-F2. The consequences of the strong oligomerization and helical propensities of the molecule are discussed and used to formulate a hypothetical model of its interaction with the mitochondrial membrane.

PubMed: 17052982
DOI: 10.1074/jbc.M606494200

Experimental method

SOLUTION NMR