Design of functional intrinsically disordered proteins.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Ankush Garg, Nicolas S González-Foutel, Maciej B Gielnik, Magnus Kjaergaard
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引用次数: 0

Abstract

Many proteins do not fold into a fixed three-dimensional structure, but rather function in a highly disordered state. These intrinsically disordered proteins pose a unique challenge to protein engineering and design: How can proteins be designed de novo if not by tailoring their structure? Here, we will review the nascent field of design of intrinsically disordered proteins with focus on applications in biotechnology and medicine. The design goals should not necessarily be the same as for de novo design of folded proteins as disordered proteins have unique functional strengths and limitations. We focus on functions where intrinsically disordered proteins are uniquely suited including disordered linkers, desiccation chaperones, sensors of the chemical environment, delivery of pharmaceuticals, and constituents of biomolecular condensates. Design of functional intrinsically disordered proteins relies on a combination of computational tools and heuristics gleaned from sequence-function studies. There are few cases where intrinsically disordered proteins have made it into industrial applications. However, we argue that disordered proteins can perform many roles currently performed by organic polymers, and that these proteins might be more designable due to their modularity.

设计功能性本征无序蛋白。
许多蛋白质并不折叠成固定的三维结构,而是在高度无序的状态下发挥作用。这些本质上无序的蛋白质给蛋白质工程和设计带来了独特的挑战:如果不对蛋白质的结构进行定制,如何才能从头开始设计蛋白质呢?在这里,我们将回顾本征无序蛋白设计这一新兴领域,重点关注其在生物技术和医学中的应用。设计目标不一定与从头设计折叠蛋白的目标相同,因为无序蛋白具有独特的功能优势和局限性。我们将重点放在本征无序蛋白具有独特功能的领域,包括无序连接体、干燥伴侣、化学环境传感器、药物输送以及生物分子凝聚物成分。功能性本征无序蛋白的设计依赖于计算工具与序列功能研究启发式方法的结合。本征无序蛋白进入工业应用的案例很少。不过,我们认为,无序蛋白质可以扮演许多目前由有机聚合物扮演的角色,而且由于其模块性,这些蛋白质可能更易于设计。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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