The mechanism of deep knot formation in proteins has been debated for the past two decades, but definitive answers are still lacking. In this review, we first describe knotted proteins from the perspective of shallow and deep knots, taking into account recent experimental and theoretical results. We focus on the folding mechanism, where this difference is most profound. We explain in more details the cotranslational knotting pathway. Then, we additionally show that proteins with extremely deep knots have a distinct mechanism of knotting from proteins with shallow knots. The approach based on treating shallow and deep knots as separate classes of molecules allow to classify them better and introduce a new paradigm of thinking about knotted proteins as such. This may in turn help to avoid ambiguities in further research.

中文翻译：

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打结蛋白质的折叠：区分浅结和深结的不同行为

在过去的二十年中，人们一直在争论蛋白质中深结形成的机制，但是仍然缺乏确切的答案。在这篇综述中，我们首先从浅结和深结的角度描述被打结的蛋白质，同时考虑到最近的实验和理论结果。我们专注于这种差异最大的折叠机制。我们将更详细地解释共翻译打结途径。然后，我们还表明，具有极深打结的蛋白质具有不同于具有浅打结的蛋白质打结的独特机制。这种基于将浅结和深结作为不同类别的分子进行处理的方法可以更好地对它们进行分类，并引入了一种新的思维方式来研究这种打结的蛋白质。反过来，这可能有助于避免在进一步研究中产生歧义。