在这里，研究人员使用隐式负设计来生成可以组装成多种复合物的 β 折叠介导的异二聚体。这些设计是稳定的、折叠的、可单独溶解的，在混合时能快速组装，并且晶体结构接近计算模型。研究人员构建了具有多达六种不同组分的线性排列的异质低聚物，支化的异质低聚物，闭合的 C4 对称双组分环，以及组装在环状同质低聚物中心枢纽上的异质低聚物，并证明这种复合物可以通过亚基交换重新配置。他们的方法为设计不对称的可重构蛋白质系统提供了一般的路线。
据介绍，经历亚基交换的不对称多蛋白复合物在生物学中发挥着核心作用，但也给设计带来了挑战，因为这些组分不仅必须包含能够实现可逆结合的界面，而且还必须在隔离时保持稳定和良好的性能。
附：英文原文
Title: Reconfigurable asymmetric protein assemblies through implicit negative design
Author: Danny D. Sahtoe, Florian Praetorius, Alexis Courbet, Yang Hsia, Basile I. M. Wicky, Natasha I. Edman, Lauren M. Miller, Bart J. R. Timmermans, Justin Decarreau, Hana M. Morris, Alex Kang, Asim K. Bera, David Baker
Issue&Volume: 2022-01-21
Abstract: Asymmetric multiprotein complexes that undergo subunit exchange play central roles in biology but present a challenge for design because the components must not only contain interfaces that enable reversible association but also be stable and well behaved in isolation. We use implicit negative design to generate β sheet–mediated heterodimers that can be assembled into a wide variety of complexes. The designs are stable, folded, and soluble in isolation and rapidly assemble upon mixing, and crystal structures are close to the computational models. We construct linearly arranged hetero-oligomers with up to six different components, branched hetero-oligomers, closed C4-symmetric two-component rings, and hetero-oligomers assembled on a cyclic homo-oligomeric central hub and demonstrate that such complexes can readily reconfigure through subunit exchange. Our approach provides a general route to designing asymmetric reconfigurable protein systems.
DOI: abj7662
Source: https://www.science.org/doi/10.1126/science.abj7662