8D86

Isoreticular, interpenetrating co-crystal of Replication Initiator Protein REPE54 and symmetrical expanded duplex (31mer) containing the cognate REPE54 sequence and an additional G-C rich sequence co-crystallized with a guest small molecule, netropsin.

Summary for 8D86

• Entry DOI: 10.2210/pdb8d86/pdb
• Related: 7u6k
• Descriptor: DNA (5'-D(A*CP*CP*CP*GP*GP*AP*CP*CP*TP*GP*TP*GP*AP*CP*AP*AP*AP*TP*TP*GP*CP*CP*CP*TP*CP*AP*GP*AP*CP*GP*G)-3'), DNA (5'-D(A*GP*GP*CP*CP*GP*TP*CP*TP*GP*AP*GP*GP*GP*CP*AP*AP*TP*TP*TP*GP*TP*CP*AP*CP*AP*GP*GP*TP*CP*CP*G)-3'), Replication initiation protein, ... (6 entities in total)
• Functional Keywords: replication initiator repe complex co-crystal, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 3
• Total formula weight: 50995.70

Authors

Orun, A.R.,Snow, C.D. (deposition date: 2022-06-07, release date: 2023-06-28, Last modification date: 2023-11-01)

Primary citation

Orun, A.R.,Shields, E.T.,Dmytriw, S.,Vajapayajula, A.,Slaughter, C.K.,Snow, C.D.
Modular Protein-DNA Cocrystals as Precise, Programmable Assembly Scaffolds.
Acs Nano, 17:13110-13120, 2023

PubMed Abstract: High-precision nanomaterials to entrap DNA-binding molecules are sought after for applications such as controlled drug delivery and scaffold-assisted structural biology. Here, we engineered protein-DNA cocrystals to serve as scaffolds for DNA-binding molecules. The designed cocrystals, isoreticular cocrystals, contain DNA-binding protein and cognate DNA blocks where the DNA-DNA junctions stack end-to-end. Furthermore, the crystal symmetry allows topology preserving (isoreticular) expansion of the DNA stack without breaking protein-protein contacts, hence providing larger solvent channels for guest diffusion. Experimentally, the resulting designed isoreticular cocrystal adopted an interpenetrating 222 lattice, a phenomenon previously observed in metal-organic frameworks (MOFs). The interpenetrating lattice crystallized dependably in the same space group despite myriad modifications at the DNA-DNA junctions. Assembly was modular with respect to the DNA inserted for expansion, providing an interchangeable DNA sequence for guest-specified scaffolding. Also, the DNA-DNA junctions were tunable, accommodating varied sticky base overhang lengths and terminal phosphorylation. As a proof of concept, we used the interpenetrating scaffold crystals to separately entrap three distinct guest molecules during crystallization. Isoreticular cocrystal design offers a route to a programmable scaffold for DNA-binding molecules, and the design principles may be applied to existing cocrystals to develop scaffolding materials.

PubMed: 37407546
DOI: 10.1021/acsnano.2c07282

Experimental method

X-RAY DIFFRACTION (3.12 Å)