Much of our current knowledge of biological chemistry is founded in the structure-function relationship, whereby sequence determines structure that determines function. Thus, the discovery that a large fraction of the proteome is intrinsically disordered, while being functional, has revolutionized our understanding of proteins and raised new and interesting questions. Many intrinsically disordered proteins (IDPs) have been determined to undergo a disorder-to-order transition when recognizing their physiological partners, suggesting that their mechanisms of folding are intrinsically different from those observed in globular proteins. However, IDPs also follow some of the classic paradigms established for globular proteins, pointing to important similarities in their behavior. In this review, we compare and contrast the folding mechanisms of globular proteins with the emerging features of binding-induced folding of intrinsically disordered proteins. Specifically, whereas disorder-to-order transitions of intrinsically disordered proteins appear to follow rules of globular protein folding, such as the cooperative nature of the reaction, their folding pathways are remarkably more malleable, due to the heterogeneous nature of their folding nuclei, as probed by analysis of linear free-energy relationship plots. These insights have led to a new model for the disorder-to-order transition in IDPs termed "templated folding," whereby the binding partner dictates distinct structural transitions en route to product, while ensuring a cooperative folding.

中文翻译：

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本质上无序的蛋白质的模板折叠。

我们目前对生物化学的许多了解都建立在结构与功能的关系中，其中顺序决定了决定功能的结构。因此，发现蛋白质组中的很大一部分是内在无序的，尽管具有功能，但这一发现彻底改变了我们对蛋白质的理解，并提出了新的有趣的问题。已经确定许多内在无序的蛋白质（IDP）在识别其生理伴侣时会经历从无序到有序的转变，这表明它们的折叠机制与球状蛋白质中观察到的内在不同。但是，IDP也遵循为球蛋白建立的一些经典范例，指出它们行为的重要相似之处。在这篇评论中 我们比较和对比球蛋白的折叠机制与结合诱导的内在无序蛋白折叠的特征。具体而言，虽然固有无序蛋白的无序变化似乎遵循球状蛋白折叠的规则，例如反应的协同性质，但由于其折叠核的异质性，它们的折叠途径具有更大的延展性，例如通过分析线性自由能关系图来探究。这些见解导致了IDP中从无序到有序过渡的新模型，称为“模板折叠”，通过该模型，结合伴侣指示了在通往产品途中的独特结构过渡，同时确保了协同折叠。