Zhang Zhiyin, Chiang Huat T, Xia Ying, Avakyan Nicole, Sonani Ravi R, Wang Fengbin, Egelman Edward H, De Yoreo James J, Pozzo Lilo D, Tezcan F Akif
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
Chem. 2025 Jun 12;11(6). doi: 10.1016/j.chempr.2024.102407. Epub 2025 Feb 10.
Host-guest interactions have been widely used to build responsive materials and molecular machines owing to their inherently dynamic nature, interaction specificity, and responsiveness to diverse stimuli. Here we have set out to exploit these advantages of host-guest chemistry in the design of dynamic protein assemblies, using a symmetric protein, RhuA, as a building block. We show that RhuA variant individually modified with β-cyclodextrin (βCD) (host) or azobenzene (guest) functionalities can specifically pair with each other to form highly ordered 1- and 2-D assemblies. Association and dissociation RhuA-RhuA assemblies can be controlled by UV and visible light as well as by small-molecule modulators of βCD-azobenzene interactions. Kinetics analyses reveal that RhuA-RhuA nanotubes assemble without a nucleation barrier, a highly unusual occurrence for helical supramolecular systems. Taken together, our findings provide a compelling example for achieving complex structural and dynamic outcomes in protein assembly through simple chemical design.
由于主客体相互作用具有内在的动态性质、相互作用特异性以及对多种刺激的响应性，它们已被广泛用于构建响应性材料和分子机器。在这里，我们着手利用主客体化学的这些优势来设计动态蛋白质组装体，使用对称蛋白质RhuA作为构建单元。我们表明，分别用β-环糊精（βCD，主体）或偶氮苯（客体）功能基团修饰的RhuA变体可以特异性地相互配对，形成高度有序的一维和二维组装体。RhuA-RhuA组装体的缔合和解离可以通过紫外线和可见光以及βCD-偶氮苯相互作用的小分子调节剂来控制。动力学分析表明，RhuA-RhuA纳米管的组装没有成核障碍，这对于螺旋超分子系统来说是非常罕见的情况。综上所述，我们的研究结果为通过简单的化学设计在蛋白质组装中实现复杂的结构和动态结果提供了一个令人信服的例子。
