柔軟なDNAを利用した新しいタンパク質結晶化技術を開発(Flexible DNA transforms protein crystallization)

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2026-07-29 ノースウェスタン大学

米国ノースウェスタン大学の研究チームは、柔軟性を持つDNA分子を利用してタンパク質の結晶化を促進する新たな手法を開発した。タンパク質の立体構造解析には高品質な結晶が不可欠であるが、多くのタンパク質は結晶化が難しく、創薬や生命科学研究の大きな課題となっている。今回の研究では、柔軟なDNA構造を足場として利用することで、タンパク質分子同士が規則正しく配置されやすくなり、従来は結晶化が困難だったタンパク質でも良質な結晶を形成できることを示した。この方法はタンパク質本来の構造や機能への影響を最小限に抑えながら結晶形成を支援できる点が特徴であり、X線結晶構造解析などによる高精度な立体構造の決定を容易にする可能性がある。研究成果は、疾患関連タンパク質や創薬標的の構造解析を加速し、新薬開発や生体分子工学の発展に貢献することが期待される。

柔軟なDNAを利用した新しいタンパク質結晶化技術を開発(Flexible DNA transforms protein crystallization)
In the new study, Chad Mirkin’s team attached short DNA strands to each protein. Image courtesy of the Mirkin Research Group

<関連情報>

DNAを用いて設計された、回折に適した超柔軟なタンパク質単結晶 Diffraction-quality, ultraflexible protein single crystals engineered with DNA

Zhenyu Han and Chad A. Mirkin
Science Advances  Published:29 Jul 2026
DOI:https://doi.org/10.1126/sciadv.aeh2948

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.


ナノ粒子をマクロな材料へと合理的に組み立てるためのDNAベースの手法 A DNA-based method for rationally assembling nanoparticles into macroscopic materials

Chad A. Mirkin,Robert L. Letsinger,Robert C. Mucic & James J. Storhoff
Nature  Accepted24 June 1996
DOI:https://doi.org/10.1038/382607a0

Abstract

COLLOIDAL particles of metals and semiconductors have potentially useful optical, optoelectronic and material properties1–4 that derive from their small (nanoscopic) size. These properties might lead to applications including chemical sensors, spectro-scopic enhancers, quantum dot and nanostructure fabrication, and microimaging methods2–4. A great deal of control can now be exercised over the chemical composition, size and polydis-persity1,2 of colloidal particles, and many methods have been developed for assembling them into useful aggregates and materials. Here we describe a method for assembling colloidal gold nanoparticles rationally and reversibly into macroscopic aggregates. The method involves attaching to the surfaces of two batches of 13-nm gold particles non-complementary DNA oligo-nucleotides capped with thiol groups, which bind to gold. When we add to the solution an oligonucleotide duplex with ‘sticky ends’ that are complementary to the two grafted sequences, the nanoparticles self-assemble into aggregates. This assembly process can be reversed by thermal denaturation. This strategy should now make it possible to tailor the optical, electronic and structural properties of the colloidal aggregates by using the specificity of DNA interactions to direct the interactions between particles of different size and composition.

生物化学工学
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