Re-engineering protein interfaces yields copper-inducible ferritin cage assembly
Re-engineering protein interfaces yields copper-inducible ferritin cage assembly
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DOI：
10.1038/nchembio.1163
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发表时间：
2013-03-01
影响因子：
14.8
通讯作者：
Tezcan, F. Akif
中科院分区：
文献类型：
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作者：
Huard, Dustin J. E.;Kane, Kathleen M.;Tezcan, F. Akif
化学控制蛋白质-蛋白质相互作用的能力将允许询问动态细胞过程，并导致更好地理解和利用自组装蛋白质结构。在这里，我们引入了一种新的工程策略反向金属模板界面重新设计（rMeTIR）——将天然蛋白质-蛋白质界面转变为仅对金属离子进行选择性响应的界面。我们应用 rMeTIR 使笼状蛋白铁蛋白的自组装可通过二价铜结合进行控制，从而可以研究分离的铁蛋白单体的结构和稳定性，证明保守的氢键相互作用在为笼组装提供几何特异性以及生理条件下笼内部的均匀化学修饰中的主要作用。值得注意的是，铜作为铁蛋白组装的结构模板，其方式与病毒衣壳形成模板的 RNA 序列高度相似。
The ability to chemically control protein-protein interactions would allow the interrogation of dynamic cellular processes and lead to a better understanding and exploitation of self-assembling protein architectures. Here we introduce a new engineering strategy reverse metal-templated interface redesign (rMeTIR)-that transforms a natural protein-protein interface into one that only engages in selective response to a metal ion. We have applied rMeTIR to render the self-assembly of the cage-like protein ferritin controllable by divalent copper binding, which has allowed the study of the structure and stability of the isolated ferritin monomer, the demonstration of the primary role of conserved hydrogen-bonding interactions in providing geometric specificity for cage assembly and the uniform chemical modification of the cage interior under physiological conditions. Notably, copper acts as a structural template for ferritin assembly in a manner that is highly reminiscent of RNA sequences that template virus capsid formation.