Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, Maryland NanoCenter, College Park, Maryland 20742, United States.
J Am Chem Soc. 2012 Aug 1;134(30):12557-64. doi: 10.1021/ja3025033. Epub 2012 Jul 18.
Three-dimensional (3D) DNA crystals have been envisioned as programmable biomaterial scaffolds for creating ordered arrays of biological and nonbiological molecules. Despite having excellent programmable properties, the linearity of the Watson-Crick B-form duplex imposes limitations on 3D crystal design. Predictable noncanonical base pairing motifs have the potential to serve as junctions to connect linear DNA segments into complex 3D lattices. Here, we designed crystals based on a template structure with parallel-stranded noncanonical base pairs. Depending on pH, the structures we determined contained all but one or two of the designed secondary structure interactions. Surprisingly, a conformational change of the designed Watson-Crick duplex region resulted in crystal packing differences between the predicted and observed structures. However, the designed noncanonical motif was virtually identical to the template when crystals were grown at pH 5.5, highlighting the motif's predictability. At pH 7.0 we observed a structurally similar variation on this motif that contains a previously unobserved C-G•G-C quadruple base pair. We demonstrate that these two variants can interconvert in crystallo in response to pH perturbations. This study spotlights several important considerations in DNA crystal design, describes the first 3D DNA lattice composed of A-DNA helical sheets, and reveals a noncanonical DNA motif that has adaptive features that may be useful for designing dynamic crystals or biomaterial assemblies.
三维（3D）DNA 晶体被设想为可编程的生物材料支架，用于创建生物和非生物分子的有序阵列。尽管具有出色的可编程特性，但沃森-克里克 B 型双螺旋的线性限制了 3D 晶体的设计。可预测的非规范碱基配对基序有可能作为连接线性 DNA 片段的连接点，形成复杂的 3D 晶格。在这里，我们设计了基于具有平行链非规范碱基对模板结构的晶体。根据 pH 值的不同，我们确定的结构包含除一个或两个设计的二级结构相互作用之外的所有相互作用。令人惊讶的是，设计的沃森-克里克双链区域的构象变化导致预测结构和观察结构之间的晶体堆积差异。然而，当在 pH 5.5 下生长晶体时，设计的非规范基序与模板几乎相同，突出了该基序的可预测性。在 pH 7.0 时，我们观察到该基序的结构相似变化，其中包含以前未观察到的 C-G•G-C 四重碱基对。我们证明这两种变体可以在结晶状态下响应 pH 扰动相互转化。这项研究强调了 DNA 晶体设计中的几个重要考虑因素，描述了第一个由 A-DNA 螺旋片组成的 3D DNA 晶格，并揭示了一种非规范 DNA 基序，该基序具有自适应特征，可能有助于设计动态晶体或生物材料组件。
