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Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Non-canonical base pairing motifs in DNA crystal design

DNA has proved to be a successful material for creation of nanoscale structures because of its inherent programmability and predictable structural features. However, the assembly of periodic three-dimensional (3D) DNA crystals is hampered by the junctions needed to connect the inherently linear Watson-Crick duplexes. Here, we examine how predictable non-canonical base pairing motifs can be used in conjunction with Watson-Crick duplexes to assemble macroscopic 3D crystals with useful nanoscale features. Parallel-stranded homopurine 5'-GGA base pairs serve as a junction region in a continuously base paired 13-mer DNA crystal (Paukstelis et al., 2004). This motif is predictable and has been used in different sequence contexts to rationally design DNA crystals with different lattice dimensions. These designed crystals have been utilized as macromolecular sieves for capturing or excluding proteins (Paukstelis, 2006). Further, we have demonstrated that a protein enzyme encapsulated in the crystal solvent channels is capable of performing catalysis. Enzyme-infused DNA crystals are capable of multiple cycles of catalysis following removal of substrate and products, and may offer potential new routes for enzyme replacement therapies or the creation of new biodegradable solid-state catalysts and sensors. A structurally similar homoparallel region, 5'-CGAA, has also been used to generate crystals that are capable of making concerted in crystallo structural transitions in response to pH perturbations (Muser & Paukstelis, 2012). These studies highlight potential uses of DNA crystals as stimuli-responsive biomaterials. Despite these successes, the ability to use non-canonical DNA motifs in crystal design is limited by both the number of available non-canonical DNA structures, and our understanding of how these structures self-assemble. To address this we have initiated a high-throughput crystallization screen of short DNA oligonucleotides to identify new non-canonical base pairing motifs and to address the broad question: How structurally diverse is DNA?

This research has been supported by NSF CAREER Award DMR-1149665

References

    Paukstelis, P.J., Nowakowski, J., Birktoft, J.J., & Seeman, N.C. (2004). Crystal structure of a continuous three-dimensional DNA lattice. Chem. Biol. 11, 1119-26.

    Paukstelis, P.J. (2006). Three-dimensional DNA crystals as molecular sieves. J. Am. Chem. Soc. 128, 6794-95.

    Muser, S.E. & Paukstelis, P.J. (2012). Three-dimensional DNA crystals with pH-responsive noncanonical junctions. J. Am. Chem. Soc. 134, 12557-64.


Chun Geng
Stephanie E. Muser
and Paul J. Paukstelis

Center for Biomolecular Structure and Organization Department of Chemistry & Biochemistry, University of Maryland College Park, MD 20742

Ph: (301) 405-9933
Fx: (301) 405-9377
Email: paukstel@umd.edu