Three hybrid systems

Licitra, E. J., and Liu, J. O. (1996). A three-hybrid system for detecting small ligand—protein receptor interactions. Proc. Natl. Acad. Sci. USA 93, 12817—12821. 

Tirade, F., Malaguti, C., Romero, F., Attar, R., Camonis, J., and Egly, J. M. (1997) A conditionally expressed third partner stabilizes or prevents the formation of a transcriptional activator in a three-hybrid system. J. Biol. Chem. 272, 22,995-22,999. 

A wide variety of library screening technologies have been developed. Two and three hybrid systems and analogous technologies have proved extremely useful for detecting pairs of interacting proteins or peptides... 

Another approach to the selection of biomolecules with novel functionalities, i.e. binding, or even enzymatic activity, is based on the yeast two- and three-hybrid system. The potential and limitations of these and related approaches are reviewed in the chapter contributed by the group of V. W. Cornish et al. 

Fig. 7.12. Structures of several of the small molecules used as Chemical Inducers of Dimerizations (CIDs) in the three-hybrid systems to date.

For molecular evolution applications, an important step will be the design of a robust bacterial small molecule three-hybrid system. 

Kley N. Chemical dimerizers and three-hybrid systems scanning the proteome for targets of organic small molecules. Chem. Biol. 2004 11 599-608. 

Figure 5 Variations on the three-hybrid method, (a) Two common variations of the reverse three-hybrid are shown. In the first, potential inhibitors are applied to a two-hybrid system, and interruption of the protein-protein contact (Xwith Y) is expected to interrupt reporter gene levels. In the other variation, proteins are expressed in the presence of a functional three-hybrid system, and successful binding displaces the activation domain (V). (b) Some three-hybrid systems have been assembled to rely on the activity of an enzyme for reporter gene activation thus, these systems can be used to identify inhibitors or to identify enzymes with desired properties, (c) A membrane-associated three-hybrid is shown schematically. In this system, STAT3 is recruited to active )ak2 by association between the "prey" (X) and the bifunctional three-hybrid probe.

Kley N. Chemical dimerizers and three-hybrid systems scanning 67. 

Receptor-dependence of the transcription read-out in a small-molecule three-hybrid system. ChemBioChem. 2002 887-895. 74. 

Henthorn DC, Jaxa-Chamiec AA, Meldmm E. A GAL4-based yeast three-hybrid system for the identification of small molecule-target protein interactions. Biochem. Pharmacol. 2002 63 1619-1628. 

Konig J, Julius C, Baumann S, Homann M, Goringer HU, Feldbmgge M. Combining SELEX and the yeast three-hybrid system for in vivo selection and classification of RNA aptamers. RNA 2007 13 614-622. 

Riley KJ, Cassiday LA, Kumar A, Maher LJ 3rd. Recognition of RNA by the p53 tumor suppressor protein in the yeast three-hybrid system. Rna 2006 12 620-630. 

Bernstein DS, Buter N, Smmpf C, Wickens M. Analyzing mRNA-protein complexes using a yeast three-hybrid system. Methods 2002 26 123-141. 

Martin F, Michel F, Zenklusen D, Muller B, Schumperli D. Positive and negative mutant selection in the human histone hairpin-binding protein using the yeast three-hybrid system. Nucleic Acids Res. 2000 28 1594-1603. 

Hook B, Bernstein D, Zhang B, Wickens M. RNA-protein interactions in the yeast three-hybrid system affinity, sensitivity, and enhanced library screening. Rna 2005 11 227-233. 

Hussey SL, Muddana SS, Peterson BR. Synthesis of a beta-estradiol-biotin chimera that potently heterodimerizes estrogen receptor and streptavidin proteins in a yeast three-hybrid system. J. Am. Chem. Soc. 2003 125 3692-3693. 

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