Mallam Anna L
St John's College and University Chemical Laboratory, Cambridge, UK.
FEBS J. 2009 Jan;276(2):365-75. doi: 10.1111/j.1742-4658.2008.06801.x. Epub 2008 Dec 10.
The issue of how a newly synthesized polypeptide chain folds to form a protein with a unique three-dimensional structure, otherwise known as the 'protein-folding problem', remains a fundamental question in the life sciences. Over the last few decades, much information has been gathered about the mechanisms by which proteins fold. However, despite the vast topological diversity observed in biological structures, it was thought improbable, if not impossible, that a polypeptide chain could 'knot' itself to form a functional protein. Nevertheless, such knotted structures have since been identified, raising questions about how such complex topologies can arise during folding. Their formation does not fit any current folding models or mechanisms, and therefore represents an important piece of the protein-folding puzzle. This article reviews the progress made towards discovering how nature codes for, and contends with, knots during protein folding, and examines the insights gained from both experimental and computational studies. Mechanisms to account for the formation of knotted structures that were previously thought unfeasible, and their implications for protein folding, are also discussed.
一条新合成的多肽链如何折叠形成具有独特三维结构的蛋白质这一问题，也就是所谓的“蛋白质折叠问题”，仍然是生命科学中的一个基本问题。在过去几十年里，人们已经收集了大量关于蛋白质折叠机制的信息。然而，尽管在生物结构中观察到了巨大的拓扑多样性，但人们认为，一条多肽链即便有可能，也极不可能“打结”形成功能性蛋白质。尽管如此，此后人们已经鉴定出了这种打结结构，这就引发了关于这种复杂拓扑结构在折叠过程中如何产生的问题。它们的形成不符合任何当前的折叠模型或机制，因此是蛋白质折叠难题的一个重要部分。本文综述了在发现自然如何编码以及在蛋白质折叠过程中如何处理打结结构方面所取得的进展，并审视了从实验研究和计算研究中获得的见解。文中还讨论了此前被认为不可行的打结结构形成机制及其对蛋白质折叠的影响。
