Tailored protein encapsulation into a DNA host using geometrically organized supramolecular interactions

Area of Science:

• Biochemistry
• Nanotechnology
• Molecular Biology

Background:

• DNA self-organization enables synthetic host creation for protein encapsulation.
• Existing DNA-protein conjugation methods limit emulation of natural host-guest systems.
• Natural systems rely on non-covalent bonds and geometrically matching interfaces.

Purpose of the Study:

• To develop a semisynthetic DNA-protein complex using only supramolecular interactions.
• To create a DNA nanocontainer that precisely encapsulates single protein molecules.
• To emulate natural host-guest systems with programmable symmetry and binding.

Main Methods:

• Decorating the inner surface of DNA origami hollow structures with multiple ligands.
• Utilizing spatially defined supramolecular interactions for complex assembly.
• Designing ligands to bind specific sites on protein surfaces with programmable range-of-action.

Main Results:

• Demonstrated one of the largest semisynthetic DNA-protein complexes formed exclusively by supramolecular interactions.
• Achieved specific host-guest recognition with 1:1 stoichiometry.
• Showcased selectivity for guest molecules based on size, enabling diffusion and maintaining short distances.

Conclusions:

• DNA nanocontainers can be rationally designed for single-molecule protein trapping in their native form.
• This approach mimics natural molecular recognition strategies.
• Anticipates a novel method for protein caging and controlled encapsulation.