Metal-Directed Design of Supramolecular Protein Assemblies.

Metal-Directed Design of Supramolecular Protein Assemblies.
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DOI:
10.1016/bs.mie.2016.05.009
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发表时间:
2016
影响因子:
--
通讯作者:
Tezcan, F. A.
Tezcan, F. A.
中科院分区:
生物学4区
文献类型:
--
作者:
Bailey, J. B.;Subramanian, R. H.;Churchfield, L. A.;Tezcan, F. A.

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由于它们在细胞信号传导、构建和生物化学中的核心作用,蛋白质-蛋白质相互作用(PPIs)和蛋白质自组装已成为分子设计和合成生物学的主要焦点。为了避免构建广泛的非共价界面(通常涉及天然PPIs和蛋白质自组装)的复杂性,我们开发了两种设计策略,金属定向蛋白质自组装(MDPSA)和金属模板界面重新设计(MeTIR)。这些策略受到金属的进化作用及其在天然PPIs中的普遍存在的启发,利用金属配位的有利特性(键合强度、方向性和可逆性),以最小的设计和工程指导蛋白质自组装。使用小单体蛋白(细胞色素cb562)作为模型构建块,我们使用MDPSA和MeTIR创建了多种功能超分子结构,其范围从结构可调的低聚物到金属蛋白复合物,这些复合物可以在活细胞中正确地自组装成新的金属酶。本文概述的设计原则和策略应该很容易适用于其他蛋白质系统,其目标是创造新的PPIs和蛋白质组件,其结构和功能尚未由自然进化产生。
Owing to their central roles in cellular signaling, construction, and biochemistry, protein-protein interactions (PPIs) and protein self-assembly have become a major focus of molecular design and synthetic biology. In order to circumvent the complexity of constructing extensive non-covalent interfaces, which are typically involved in natural PPIs and protein self-assembly, we have developed two design strategies, Metal-Directed Protein Self-Assembly (MDPSA) and Metal-Templated Interface Redesign (MeTIR). These strategies, inspired by both the proposed evolutionary roles of metals and their prevalence in natural PPIs, take advantage of the favorable properties of metal coordination (bonding strength, directionality, and reversibility) to guide protein self-assembly with minimal design and engineering. Using a small, monomeric protein (cytochrome cb562) as a model building block, we employed MDPSA and MeTIR to create a diverse array of functional supramolecular architectures which range from structurally tunable oligomers to metalloprotein complexes that can properly self-assemble in living cells into novel metalloenzymes. The design principles and strategies outlined herein should be readily applicable to other protein systems with the goal of creating new PPIs and protein assemblies with structures and functions not yet produced by natural evolution.
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