2hn8
From Proteopedia
(New page: 200px<br /><applet load="2hn8" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hn8" /> '''Structural characterization and oligomerizat...) |
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'''Structural characterization and oligomerization of PB1-F2, a pro-apoptotic influenza A virus protein'''<br /> | '''Structural characterization and oligomerization of PB1-F2, a pro-apoptotic influenza A virus protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Recently, a novel 87-amino acid influenza A virus protein with | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2HN8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 2HN8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HN8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: pro-apoptotic mitochondrial targeting protein]] | [[Category: pro-apoptotic mitochondrial targeting protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:43:33 2008'' |
Revision as of 15:43, 21 February 2008
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Structural characterization and oligomerization of PB1-F2, a pro-apoptotic influenza A virus protein
Overview
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.
About this Structure
2HN8 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Structural characterization and oligomerization of PB1-F2, a proapoptotic influenza A virus protein., Bruns K, Studtrucker N, Sharma A, Fossen T, Mitzner D, Eissmann A, Tessmer U, Roder R, Henklein P, Wray V, Schubert U, J Biol Chem. 2007 Jan 5;282(1):353-63. Epub 2006 Oct 19. PMID:17052982
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