Controlling a substrate-binding geometry of ribonucleopeptide receptor.

ABSTRACT

We describe here a novel strategy to create a ribonucleopeptide (RNP) receptor with defined substrate-binding geometry. RNP library was generated by introducing randomized nucleotide sequences in the RNA subunit of the structurally well-defined complex of RRE-RNA and the Rev peptide by a structure-based design. ATP-binding RNP receptors were selected from the RNP library by in vitro selection. The ATP-binding RNP receptors had RNA sequences varying in the location of the consensus sequence within the randomized nucleotide region. Each RNA subunit was expected to form a ligand-binding pocket with a unique geometry to the N-terminal of the Rev peptide. We have developed a selection strategy to select an ATP-binding receptor with a defined binding geometry by utilizing an ATP-Rev peptide conjugate.