Complex lasso: new entangled motifs in proteins

Niemyska, Wanda; Dąbrowski-Tumański, Paweł; Kadlof, Michal; Haglund, Ellinor; Sułkowski, Piotr; Sułkowska, Joanna I.

doi:10.1038/srep36895

Cited by 87 publications

(119 citation statements)

References 53 publications

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“…To identify stable links in proteins, we analyzed their structure and used the method of spanning the (triangulated) minimal surface (17,18). A segment of a protein chain forms a covalent loop if the ends of the segment are connected by a covalent bond (e.g., disulfide bridges).…”

Section: Search For Linksmentioning

confidence: 99%

“…A segment of a protein chain forms a covalent loop if the ends of the segment are connected by a covalent bond (e.g., disulfide bridges). Such a covalent loop can be pierced by a protein tail, thereby forming a complex lasso structure (17) (Fig. 2).…”

Section: Search For Linksmentioning

confidence: 99%

“…2). The indexes of the cysteines are known from the protein structure, whereas indexes of loop-piercing residues can be determined from minimal surface analysis used in the classification of lasso proteins (17,18). This method is general and can be applied to various intramolecular contacts.…”

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confidence: 99%

“…To date, the only known simple protein links are designed p53 protein catenanes (15) (with the backbones of both chains artificially closed, forming linked loops) and a thermophilic two-chain complex (16) (with linked loops formed by the backbones closed via disulfide bridges). However, the discovery of a wide class of complex lasso proteins (17,18), in which a chain pierces a covalently closed loop ( Fig. 1), opens a unique possibility of defining and identifying links.…”

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confidence: 99%

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Topological knots and links in proteins

Dąbrowski-Tumański

Sułkowska

2017

Proc. Natl. Acad. Sci. U.S.A.

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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. In this work, we go one step further and search for links-entangled structures, more complex than knots, which consist of several components. We derive conditions that proteins need to meet to be able to form links. We search through the entire Protein Data Bank and identify several sequentially nonhomologous chains that form a Hopf link and a Solomon link. We relate topological properties of these proteins to their function and stability and show that the link topology is characteristic of eukaryotes only. We also explain how the presence of links affects the folding pathways of proteins. Finally, we define necessary conditions to form Borromean rings in proteins and show that no structure in the Protein Data Bank forms a link of this type.folding | catenanes | slipknot | lasso | disulphide bridge K notted proteins have been identified in all kingdoms of life, in organisms separated even by 1 billion years of evolution (1-5). High conservation (5) of knotted motifs and their location (usually) in enzymatic active sites indicates that knots are crucial for protein function. Over 1,300 knotted or slipknotted (shoelace-type) structures, including the trefoil (31), figure-eight (41), three-twist (52), and Stevedore's (61) knots (4, 6, 7), have been deposited in the Protein Data Bank (PDB) to date according to KnotProt (8).Mathematically, a knot is defined as an embedding of a circle into a 3D space. A link is a generalization of a knot, defined as an embedding of a finite set of circles. The simplest examples of links are, e.g., the Hopf link and the Solomon link ( Fig. 1, Center). Links have been found in DNA (9, 10) and have been synthesized in template synthesis (11,12). In proteins, the first attempts to identify links were made by Mislow (13,14). In his approach, however, the link-forming loops were defined either by including interaction with a metal ion (noncovalent loop) or by at least two disulfide bonds for each (covalent) loop. The links formed by covalent loops, each closed by one disulfide bridge only, were considered "unlikely to lead to knots or links" (ref. 14, p. 4,202) by Mislow and therefore hardly examined. Moreover, all of the structures were scanned only by "visual examination of their 3D structures" (ref. 14, p. 4,202). To date, the only known simple protein links are designed p53 protein catenanes (15) (with the backbones of both chains artificially closed, forming linked loops) and a thermophilic two-chain complex (16) (with linked loops formed by the backbones closed via disulfide bridges). However, the discovery of a wide class of complex lasso proteins (17, 18), in which a chain pierces a covalently closed loop (Fig. 1), opens a unique possibility of defining and identifying links. Such links (or more formally, pretzelanes) are defined using covalent loops closed by disulfide bridges in a single-protein cha...

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Section: Search For Linksmentioning

confidence: 99%

Section: Search For Linksmentioning

confidence: 99%

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Topological knots and links in proteins

Dąbrowski-Tumański

Sułkowska

2017

Proc. Natl. Acad. Sci. U.S.A.

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116

100

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“…Non-trivial structures identified in proteins with complex topologies include (open) knots and slipknots (1), complex lassos (2,3), cysteine knots (4) and various other structures defined by taking into account protein-metal bonds (5,6). Their function still puzzles researchers, but their statistical analysis is facilitated by various databases (7–10).…”

Section: Introductionmentioning

confidence: 99%

LinkProt: a database collecting information about biological links

et al. 2016

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Protein chains are known to fold into topologically complex shapes, such as knots, slipknots or complex lassos. This complex topology of the chain can be considered as an additional feature of a protein, separate from secondary and tertiary structures. Moreover, the complex topology can be defined also as one additional structural level. The LinkProt database (http://linkprot.cent.uw.edu.pl) collects and displays information about protein links — topologically non-trivial structures made by up to four chains and complexes of chains (e.g. in capsids). The database presents deterministic links (with loops closed, e.g. by two disulfide bonds), links formed probabilistically and macromolecular links. The structures are classified according to their topology and presented using the minimal surface area method. The database is also equipped with basic tools which allow users to analyze the topology of arbitrary (bio)polymers.

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