Constructing protein polyhedra via orthogonal chemical interactions
Constructing protein polyhedra via orthogonal chemical interactions
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DOI：
10.1038/s41586-019-1928-2
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发表时间：
2020-01-22
期刊：
影响因子：
64.8
通讯作者：
Tezcan, F. Akif
中科院分区：
文献类型：
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作者：
Golub, Eyal;Subramanian, Rohit H.;Tezcan, F. Akif
许多蛋白质天然存在为对称的均聚物或均聚物（1）。这种蛋白质组装体的新兴结构和功能特性激发了生物分子设计的广泛努力（2-5）。由于蛋白质是由核糖体合成的，因此蛋白质本身是不对称的。因此，它们必须获得多个表面补丁，这些补丁选择性地结合以产生形成高阶结构所需的不同对称元素（1，6）-这对蛋白质设计来说是一项艰巨的任务。在这里，我们解决这个问题，使用无机化学方法，从而多种模式的蛋白质-蛋白质相互作用和对称性，同时实现选择性，“一锅”软，硬金属离子的协调。我们表明，适当修改与生物启发的异羟肟酸基团和锌结合基序的单体蛋白质（原聚体）组装通过并发的Fe 3+和Zn 2+协调成离散的十二聚体和六聚体笼。我们的笼非常类似于天然多面体蛋白质结构（7，8），据我们所知，在设计的系统（9-13）中是独特的，因为它们具有紧密堆积的外壳，没有大的孔。同时，由于它们在最小的蛋白质间键合足迹上的异质结构，它们可以组装和分解以响应不同的刺激。化学计量范围从[2 Fe：9 Zn：6 protomers]到[8 Fe：21 Zn：12 protomers]，这些蛋白质笼代表了一些组成上最复杂的蛋白质骨架-或无机配位复合物-通过design.An无机化学方法来生物分子设计，可以同时促进蛋白质相互作用的对称性和多种模式。
Many proteins exist naturally as symmetrical homooligomers or homopolymers(1). The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design(2-5). As synthesized by ribosomes, proteins are inherently asymmetric. Thus, they must acquire multiple surface patches that selectively associate to generate the different symmetry elements needed to form higher-order architectures(1,6)-a daunting task for protein design. Here we address this problem using an inorganic chemical approach, whereby multiple modes of protein-protein interactions and symmetry are simultaneously achieved by selective, 'one-pot' coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and zinc-binding motifs assembles through concurrent Fe3+ and Zn2+ coordination into discrete dodecameric and hexameric cages. Our cages closely resemble natural polyhedral protein architectures(7,8) and are, to our knowledge, unique among designed systems(9-13) in that they possess tightly packed shells devoid of large apertures. At the same time, they can assemble and disassemble in response to diverse stimuli, owing to their heterobimetallic construction on minimal interprotein-bonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomers] to [8 Fe:21 Zn:12 protomers], these protein cages represent some of the compositionally most complex protein assemblies-or inorganic coordination complexes-obtained by design.An inorganic chemical approach to biomolecular design is used to generate 'cages' that can simultaneously promote symmetry and multiple modes of protein interactions.