Twenty years after their discovery, knots in proteins are now quite well understood. They are believed to be functionally advantageous and provide extra stability to protein chains. Recently we went one step further and found that proteins can be even more entangled than knots – they can from lassos and links, which consist of several components. During the talk I will discuss conditions that proteins need to meet to be able to form these types of entanglement. Based on the search through the whole Protein Data Bank we identified several sequentially nonhomologous chains that form a Hopf link, a Solomon link, and various types of lassos. I will show that topological properties of these proteins are related to their function and stability, for example the simplest lasso is characteristic lasso type for antimicrobial proteins, and supercoiling topology for adhesive proteins. I will also explain how the presence of links and lassos affects folding pathways of proteins.<br/>Finally, the possibility to use a lasso typology to construct biological molecular machines, similarly to rotaxanes, will be discussed. Lasso-peptides such as microcin J25 are examples of rotaxane substructure, which have been found in naturally occurring peptides. Since lassos found in proteins are even more complex, this allows to mechanically interlock molecular architectures in many other ways.

Entanglement in protein structures – knots, lassos and links: Applications in medicine

255th National Meeting (2018)

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