小柯机器人

利用正交化学作用构建蛋白质多面体
2020-01-28 22:51

美国加州大学圣迭戈分校F. Akif Tezcan团队取得一项新进展,他们通过正交化学相互作用构建出蛋白质多面体。相关论文2020年1月22日在线发表于《自然》杂志。

据研究人员介绍,许多蛋白质天然以对称均聚物或均聚物的形式存在。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方面的广泛工作。由核糖体合成的蛋白质本质上是不对称的。因此,他们必须获得多个表面斑块,从而可以选择性地结合以产生形成更高阶结构所需的不同对称元素,这是蛋白质设计的难题。
 
研究人员使用无机化学方法解决了这个问题,通过软金属和硬金属离子的选择性“一站式”配位,同时实现了多种模式的蛋白质-蛋白质相互作用和对称性。研究人员表明,通过生物学启发的异羟肟酸酯基团和锌结合基序组件适当修饰的单体蛋白(即protomer)能够通过同时存在的Fe3+和Zn2+配位成不同的十二聚体和六聚体笼。研究人员认为,这些笼子非常类似于天然的多面体蛋白结构并且在设计的系统中是独特的,即外壳紧密,没有大的缝隙。同时,由于它们在最小的蛋白间键合足迹上具有异双金属结构,因此它们可以响应各种刺激而组装和拆卸。从[2 Fe:9 Zn:6原聚体]到[8 Fe:21 Zn:12原聚体]的化学计量比,这些蛋白笼代表了某些通过设计获得的组成上最复杂的蛋白装配体或无机配位复合物。
 
附:英文原文

Title: Constructing protein polyhedra via orthogonal chemical interactions

Author: Eyal Golub, Rohit H. Subramanian, Julian Esselborn, Robert G. Alberstein, Jake B. Bailey, Jerika A. Chiong, Xiaodong Yan, Timothy Booth, Timothy S. Baker, F. Akif Tezcan

Issue&Volume: 2020-01-22

Abstract: Many proteins exist naturally as symmetrical homooligomers or homopolymers1. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design2,3,4,5. 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 architectures1,6—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 architectures7,8 and are, to our knowledge, unique among designed systems9,10,11,12,13 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.

DOI: 10.1038/s41586-019-1928-2

Source: https://www.nature.com/articles/s41586-019-1928-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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