A method is developed to use selective aptamer binding to direct the self-assembly of proteins on rationally designed nanostructures into periodical linear arrays. THey system developed here opens u opportunity for constructing nanoscale protein arrays in programmable fashion. The Self-assembling system could accommodate other aptamer sequences to construct 2-D or 3-D protein arrays. DNA templated protein arrays, with predictable control of nanometer preceision, could lead to single molecule proteomics detection when individual proteins are placed at unique addresses on the nanoarray and further detected by single molecule imaging techniques. It is also possible to change the relative positions of proteins in real time whichould enable the study of porximity effects of protein-portein interactions.We demonstrated the first use of selective DNA aptamer binding as a robust platform to link proteins to periodic sites of a self-assembled DNA array. They system developed here employs three components: 1) a rationally designed DNA nanostructure that self0assembles into highly-ordered spatial lattices by virtue of specific annealing of complementary sticky ends. 2) a DNA docking site containing aptamer sequence which will tether the protein of interest to the DNA lattice; 3) the protein to be displayed on a self-assembled DNA latticeThe DNA nanostrucure-aptamer directed self-assembly of protein array possesses the following advantageous feature; 1) The DNA tiling self-assembly has been demonstrated to be programmable. A rich set of DNA tiles and lattices with different geometry and patterns can be achieved by essentially varying the tiling design and sticky-end associations. 2) Both DNA tiles and aptamers are composed of oligonucleotides, thus they are compatible to each other. 3) New protein binding aptamers can be generated though automated process. 4) DNA nanostructure displayed aptamers are not just limited to proteins, they can be extended to bind other ligands.
|Published - May 6 2005