Structural characterization of HBXIP: the protein that interacts with the anti-apoptotic protein survivin and the oncogenic viral protein HBx.
Hepatitis B X-interacting protein (HBXIP) is a ubiquitous protein that was originally identified as a binding partner of the hepatitis B viral protein HBx. HBXIP is also thought to serve as an anti-apoptotic cofactor of survivin, promoting the suppression of pro-caspase-9 activation. Here were port the crystal structure of the shortest isoform of HBXIP (91 aa long,∼11 kDa) at 1.5 Å resolution. HBXIP crystal shows a monomer per asymmetric unit, with a profilin-like fold which is common to a super family of proteins, the Roadblock/LC7 domain family involved in protein-protein interactions. Based on this fold, we propose that HBXIP can form a dimer that can indeed be found in the crystal when symmetric molecules are generated around the asymmetric unit. This dimer shows an extended β-sheet area formed by 10 anti-parallel β-strands from both subunits. Another interesting aspect of the proposed HBXIP dimer interface is the presence of a small leucine zipper between the two α2 helices of each monomer. In solution, the scattering curve obtained by small-angle X-ray scattering for the sample used for crystallization indicates that the protein is dimeric form in solution. The fit between the experimental small angle X-ray scattering curve and the back calculated curves for two potential crystal dimers shows a significant preference for the Roadblock/LC7 fold dimer model. Moreover, the HBXIP crystal structure represents a step towards understanding the cellular role of HBXIP.
Institut de Biologie Structurale J.-P. Ebel, UMR 5075, Grenoble Cedex 1, France. isabel.garcia@ibs.fr
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Garcia-Saez
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Lacroix
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Blot
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Gabel
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Skoufias
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018360:Crystallography, X-Ray; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D006515:Hepatitis B virus; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009857:Oncogenes; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D000077022:Survivin; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; C110719:LAMTOR5 protein, human; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein