Woolfson Derek N
School of Chemistry, University of Bristol, BS8 1TS, Bristol, UK.
School of Biochemistry, University of Bristol, BS8 1TD, Bristol, UK.
Subcell Biochem. 2017;82:35-61. doi: 10.1007/978-3-319-49674-0_2.
α-Helical coiled coils are ubiquitous protein-folding and protein-interaction domains in which two or more α-helical chains come together to form bundles. Through a combination of bioinformatics analysis of many thousands of natural coiled-coil sequences and structures, plus empirical protein engineering and design studies, there is now a deep understanding of the sequence-to-structure relationships for this class of protein architecture. This has led to considerable success in rational design and what might be termed in biro de novo design of simple coiled coils, which include homo- and hetero-meric parallel dimers, trimers and tetramers. In turn, these provide a toolkit for directing the assembly of both natural proteins and more complex designs in protein engineering, materials science and synthetic biology. Moving on, the increased and improved use of computational design is allowing access to coiled-coil structures that are rare or even not observed in nature, for example α-helical barrels, which comprise five or more α-helices and have central channels into which different functions may be ported. This chapter reviews all of these advances, outlining improvements in our knowledge of the fundamentals of coiled-coil folding and assembly, and highlighting new coiled coil-based materials and applications that this new understanding is opening up. Despite considerable progress, however, challenges remain in coiled-coil design, and the next decade promises to be as productive and exciting as the last.
α-螺旋卷曲螺旋是普遍存在的蛋白质折叠和蛋白质相互作用结构域，其中两条或多条α-螺旋链聚集在一起形成束状结构。通过对数千个天然卷曲螺旋序列和结构进行生物信息学分析，并结合实证性蛋白质工程和设计研究，现在人们对这类蛋白质结构的序列与结构关系有了深入理解。这在简单卷曲螺旋的合理设计以及所谓的笔端从头设计方面取得了相当大的成功，这些简单卷曲螺旋包括同聚和异聚平行二聚体、三聚体和四聚体。相应地，这些为指导天然蛋白质的组装以及蛋白质工程、材料科学和合成生物学中更复杂的设计提供了一个工具包。接着，计算设计的更多应用和改进使得能够获得自然界中罕见甚至未观察到的卷曲螺旋结构，例如α-螺旋桶，它由五个或更多α-螺旋组成，并具有可引入不同功能的中央通道。本章回顾了所有这些进展，概述了我们对卷曲螺旋折叠和组装基本原理认识的改进，并强调了基于卷曲螺旋的新材料以及这种新认识所带来的新应用。然而，尽管取得了相当大的进展，卷曲螺旋设计仍面临挑战，未来十年有望与过去十年一样富有成效且令人兴奋。
