Lin Yu-Ru, Koga Nobuyasu, Tatsumi-Koga Rie, Liu Gaohua, Clouser Amanda F, Montelione Gaetano T, Baker David
Department of Biochemistry, University of Washington and Howard Hughes Medical Institute, Seattle, WA 98195;
Department of Biochemistry, University of Washington and Howard Hughes Medical Institute, Seattle, WA 98195; Research Center of Integrative Molecular Systems, Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, Aichi 444-8585, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan;
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5478-85. doi: 10.1073/pnas.1509508112. Epub 2015 Sep 22.
We recently described general principles for designing ideal protein structures stabilized by completely consistent local and nonlocal interactions. The principles relate secondary structure patterns to tertiary packing motifs and enable design of different protein topologies. To achieve fine control over protein shape and size within a particular topology, we have extended the design rules by systematically analyzing the codependencies between the lengths and packing geometry of successive secondary structure elements and the backbone torsion angles of the loop linking them. We demonstrate the control afforded by the resulting extended rule set by designing a series of proteins with the same fold but considerable variation in secondary structure length, loop geometry, β-strand registry, and overall shape. Solution NMR structures of four designed proteins for two different folds show that protein shape and size can be precisely controlled within a given protein fold. These extended design principles provide the foundation for custom design of protein structures performing desired functions.
我们最近描述了通过完全一致的局部和非局部相互作用来设计理想蛋白质结构的一般原则。这些原则将二级结构模式与三级堆积基序联系起来，并能够设计不同的蛋白质拓扑结构。为了在特定拓扑结构内实现对蛋白质形状和大小的精细控制，我们通过系统分析连续二级结构元件的长度和堆积几何形状以及连接它们的环的主链扭转角之间的相互依存关系，扩展了设计规则。我们通过设计一系列具有相同折叠但二级结构长度、环几何形状、β链排列和整体形状有显著差异的蛋白质，展示了由此产生的扩展规则集所提供的控制。两种不同折叠的四种设计蛋白质的溶液核磁共振结构表明，在给定的蛋白质折叠内可以精确控制蛋白质的形状和大小。这些扩展的设计原则为定制设计执行所需功能的蛋白质结构奠定了基础。
