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  • An avidin-like domain that does not bind biotin is adopted for oligomerization by the extracellular mosaic protein fibropellin.
    Protein science : a publication of the Protein Society, 2005
    Co-Authors: Itai Yanai, Charles R. Cantor, Xiahui Zhu, Zhiping Weng
    Abstract:

    The protein avidin found in egg white seems optimized for binding the small vitamin biotin as a stable homotetramer. Indeed, along with its streptavidin ortholog in the bacterium Streptomyces Avidinii, this protein shows the strongest known noncovalent bond of a protein with a small ligand. A third known member of the avidin family, as similar to avidin as is streptavidin, is found at the C-terminal ends of the multidomain fibropellin proteins found in sea urchin. The fibropellins form a layer known as the apical lamina that surrounds the sea urchin embryo throughout development. Based upon the structure of avidin, we deduced a structural model for the avidin-like domain of the fibropellins and found that computational modeling predicts a lack of biotin binding and the preservation of tetramerization. To test this prediction we expressed and purified the fibropellin avidin-like domain and found it indeed to be a homotetramer incapable of binding biotin. Several lines of evidence suggest that the avidin-like domain causes the entire fibropellin protein to tetramerize. We suggest that the presence of the avidin-like domain serves a structural (tetrameric form) rather than functional (biotin-binding) role and may therefore be a molecular instance of exaptation-the modification of an existing function toward a new function. Finally, based upon the oligomerization of the avidin-like domain, we propose a model for the overall structure of the apical lamina.

  • [19] Streptavidin-containing chimeric proteins: design and production
    Methods in enzymology, 2000
    Co-Authors: Takeshi Sano, Charles R. Cantor
    Abstract:

    Publisher Summary This chapter presents the design and production of streptavidin-containing chimeric proteins. It also describes the general protocols for expressing streptavidin-containing chimeras in E. coli by using the bacteriophage T7 expression system and procedures for purifying and characterizing expressed streptavidin-containing chimeric proteins. Streptavidin is a tetrameric protein produced by the bacterium Streptomyces Avidinii , and it has an estimated biotin-binding affinity ( K d ) at 10 –14 M , similar to that of avidin. Its great similarity to avidin, including the biotin-binding and structural characteristics, resulted in the naming of this protein as the Streptomyces equivalent of avidin. The tetrameric structure is essential for its extremely tight biotin-binding affinity because intersubunit contacts to biotin, made by an adjacent subunit through a subunit-subunit interface, have a significant contribution to the biotin-binding site. The three-dimensional structured streptavidin suggests that, without significant modifications, streptavidin would not be able to form a stable, functional molecule in a dimeric or monomeric form, although a dimeric streptavidin with reduced biotin-binding affinity and stability has already been produced. When a partner protein is fused to streptavidin, the resulting streptavidin-containing chimeric protein forms a tetramer via its streptavidin moiety, making the fused partner protein also tetrameric.

  • Genetic engineering of streptavidin, a versatile affinity tag
    Journal of chromatography. B Biomedical sciences and applications, 1998
    Co-Authors: Takeshi Sano, Sandor Vajda, Charles R. Cantor
    Abstract:

    Streptavidin, a tetrameric protein produced by Streptomyces Avidinii, has been used as a useful, versatile affinity tag in a variety of biological applications. The efficacy of streptavidin is derived from its extremely high binding affinity for the vitamin biotin. For the last several years, we have used genetic engineering as a primary means to enhance the properties of streptavidin and to expand the application of streptavidin as an affinity tag. In this review, we describe several genetically engineered streptavidin variants, which include a streptavidin with a reduced biotin-binding affinity, a dimeric streptavidin, and a fusion protein between streptavidin and protein A, along with their potential applications in biological science.

  • Streptavidin-based conditional lethal system for biological containment of Pseudomonas putida
    Studies in Environmental Science, 1997
    Co-Authors: Charles R. Cantor, Charlene M. Mello, Przemyslaw Szafranski, Cassandra L Smith, Takeshi Sano, David L Kaplan
    Abstract:

    The soil bacterium Pseudomonas putida can potentially be applied in bioremediation of areas polluted with aromatic hydrocarbon-based organic solvents and petroleum. However, its use in the open environment has been hindered so far by the lack of reliable survival-control functions. To increase the predictability of P. putida, a novel cell suicide system was constructed, based on triple control of the expression of the lethal Streptomyces Avidinii streptavidin gene (stv) coupled with P. putida TOL plasmid-derived Pm/xylS regulatory circuit. In the absence of hydrocarbon pollutants (3-methylbenzoate in described in vitro studies), all but one in 107 to 108 of genetically modified bacteria commits suicide. The stv-based conditional lethal design can thus effectively limit the spread of released microorganisms strictly to polluted localities and keep them alive only as long as the amount of contaminants keeps above a level determined by the sensitivity of their interaction with the XylS protein.

  • A new approach for containment of microorganisms: Dual control of streptavidin expression by antisense RNA and the T7 transcription system
    Proceedings of the National Academy of Sciences of the United States of America, 1997
    Co-Authors: Przemyslaw Szafranski, Charlene M. Mello, Cassandra L Smith, Takeshi Sano, David L Kaplan, Charles R. Cantor
    Abstract:

    The use of microorganisms in the open environment would be of less concern if they were endowed with programmed self-destruction mechanisms. Here, we propose a new genetic design to increase the effectiveness of cell suicide systems. It ensures very tight control of the derepression of cell death by the combination of the bacteriophage T7 RNA polymerase-lysozyme system and an inducible synthesis of antisense RNA and the Escherichia coli LacI repressor. Functionality of this regulatory concept was tested by applying it to containment of Gram-negative bacteria, based on the conditional expression of the lethal Streptomyces Avidinii streptavidin gene. Toxicity of streptavidin is derived from its exceptionally high binding affinity for an essential prosthetic group, d-biotin. The entire construct was designed to allow the soil bacterium Pseudomonas putida to survive only in the presence of aromatic hydrocarbons and their derivatives which it can degrade. Under favorable growth conditions, clones escaping killing appeared at frequencies of only 10−7–10−8 per cell per generation. The general requirement for biotin through the living world should make streptavidin-based conditional lethal designs applicable to a broad range of containment strategies.