Diffraction-quality, ultraflexible protein single crystals engineered with DNA

Han, Zhenyu [Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.] (ORCID:0000000337989345); Mirkin, Chad A. [Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.] (ORCID:0000000266347627)

doi:10.1126/sciadv.aeh2948

DOE OSTI · 3685242

Diffraction-quality, ultraflexible protein single crystals engineered with DNA

Han, Zhenyu [Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.] (ORCID:0000000337989345)·Mirkin, Chad A. [Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.] (ORCID:0000000266347627)

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Abstract

DNA-functionalized colloidal nanoparticles assemble through flexible, nanoscale DNA hybridization interactions that limit atomic-level structural order. Here, we report a valence-centric strategy that enables DNA-bonded, protein single crystals with unconventional mechanical properties. An octameric enzyme, glutarate L-2-hydroxylase, was site- and number-selectively conjugated with eight self-complementary single-stranded DNA, yielding octavalent molecular bonds. The resulting conjugate assembled into the designed body-centered tetragonal crystals that diffracted to 1.42- to 2.61-angstrom resolution, with contacts mediated by B-form DNA helices spanning 17 to 25 angstroms. Increasing oligonucleotide length induces anisotropic lattice expansion while preserving atomic periodicity, even with partial DNA occupancy. Mechanistic studies suggest that the dynamic motion of unhybridized DNA facilitates crystallization, analogous to fluctuating electron clouds in atomic bonding. Compared with native protein crystals, DNA-hybridized crystals are 23-fold softer. These results challenge the assumption that flexibility is incompatible with structural order and establish a programmable framework for biomolecular crystallization and nanomaterials engineering with atomic precision.

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Han, Zhenyu [Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.] (ORCID:0000000337989345), Mirkin, Chad A. [Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.; International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208, USA.; Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA.] (ORCID:0000000266347627). 2026-07-31. Diffraction-quality, ultraflexible protein single crystals engineered with DNA. https://doi.org/10.1126/sciadv.aeh2948

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