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Blueprinting extendable nanomaterials with standardized protein blocks
Nature ( IF 64.8 ) Pub Date : 2024-03-13 , DOI: 10.1038/s41586-024-07188-4
Timothy F. Huddy , Yang Hsia , Ryan D. Kibler , Jinwei Xu , Neville Bethel , Deepesh Nagarajan , Rachel Redler , Philip J. Y. Leung , Connor Weidle , Alexis Courbet , Erin C. Yang , Asim K. Bera , Nicolas Coudray , S. John Calise , Fatima A. Davila-Hernandez , Hannah L. Han , Kenneth D. Carr , Zhe Li , Ryan McHugh , Gabriella Reggiano , Alex Kang , Banumathi Sankaran , Miles S. Dickinson , Brian Coventry , T. J. Brunette , Yulai Liu , Justas Dauparas , Andrew J. Borst , Damian Ekiert , Justin M. Kollman , Gira Bhabha , David Baker

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures1. Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight ‘train track’ assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence–structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to ‘back of an envelope’ architectural blueprints.



中文翻译:

用标准化蛋白质块绘制可延伸纳米材料的蓝图

木屋框架由许多不同的木材块组成,但由于这些积木的规则性,可以使用简单的几何原理来设计结构。相比之下,多组分蛋白质组装体的设计要复杂得多,这主要是由于蛋白质结构的不规则形状1。在这里,我们描述了符合特定几何标准的可延伸的线性、弯曲和有角度的蛋白质构建块,以及块间相互作用;使用这些块设计的组件继承了它们的可扩展性和常规交互表面,使它们能够通过改变模块数量来扩展或收缩,并通过辅助支柱进行加固。使用 X 射线晶体学和电子显微镜,我们验证了纳米材料设计,从可同心嵌套的简单多边形和圆形低聚物,到大型多面体纳米笼和具有可重新配置尺寸和几何形状且可轻松绘制蓝图的无界直线“火车轨道”组件。由于蛋白质结构和序列结构关系的复杂性,以前不可能通过将蛋白质主链故意放置到空白的三维画布上来构建大型蛋白质组装体。我们的设计平台具有简单性和几何规律性,现在可以根据“信封背面”的建筑蓝图构建蛋白质纳米材料。

更新日期:2024-03-16
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