Heterobimetallic Base Pair Programming in Designer 3D DNA Crystals

Area of Science:

• Bioinorganic Chemistry
• Nanotechnology
• Structural Biology

Background:

• Metal-mediated DNA (mmDNA) offers a route to integrate bioinorganic and electronic functionalities into DNA constructs.
• Programmable metal chelation between pyrimidine base pairs is governed by various chemical and biophysical forces.

Purpose of the Study:

• To develop a crystallographic method for capturing metal binding modes in DNA across varying pH.
• To elucidate the structural basis of metal-DNA interactions at the atomic level.

Main Methods:

• Utilized a three-dimensional (3D) DNA tensegrity triangle motif for crystallization.
• Employed anomalous scattering techniques to capture single- and multi-metal binding events.
• Determined 28 biomolecular structures to analyze metal-mediated DNA reactions under different pH conditions.

Main Results:

• Observed increasing occupancy of silver(I) in T-T and U-U pairs at elevated pH.
• Successfully captured both silver(I) and mercury(II) within the same base pair, isolating titration points for homo- and heterometal binding.
• Determined the structure of C-C pairs with silver(I) and mercury(II), and T-T pairs with cadmium(II) and mercury(II) at high pH.

Conclusions:

• Demonstrated a precise method for capturing heterobimetallic DNA chemistry at the sub-nanometer scale.
• The developed crystallographic approach enables atomistic design for advanced mmDNA-based nanodevices.
• This work paves the way for sophisticated nanotechnologies leveraging controlled metal-DNA interactions.