Protein sequences encoding three common small folds (3α, β-grasp, and α/β-plait) were connected in a network with high-identity intersections, termed nodes. The structures of proteins around nodes were determined using NMR spectroscopy and analyzed for stability and binding function. To generate nodes, the amino acid sequence encoding a shorter fold (3α or β-grasp) is embedded in the structure of the ~50% longer α/β-plait fold and a new sequence is designed that satisfies two sets of native interactions. This leads to protein pairs with a 3α or β-grasp fold in the shorter form but an α/β-plait fold in the longer form. Further, embedding smaller antagonistic folds in longer folds creates critical states in the longer folds such that single amino acid substitutions can switch both their fold and function. This suggests that abrupt fold switching may be a mechanism of evolving new protein structures and functions.

中文翻译：

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蛋白质折叠转换网络的设计和表征

编码三个常见小折叠（3α、β-grasp 和 α/β-plait）的蛋白质序列连接在一个具有高同一性交叉点的网络中，称为节点。使用核磁共振光谱确定节点周围蛋白质的结构，并分析其稳定性和结合功能。为了生成节点，将编码较短折叠（3α 或 β-grasp）的氨基酸序列嵌入到长约 50% 的 α/β-褶皱折叠的结构中，并设计了一个满足两组天然相互作用的新序列。这导致蛋白质对具有较短形式的 3α 或 β-grasp 折叠，但较长形式的 α/β-褶皱折叠。此外，将较小的拮抗折叠嵌入较长的折叠中会在较长的折叠中产生临界状态，这样单个氨基酸取代就可以改变它们的折叠和功能。