LassoProt: server to analyze biopolymers with lassos

Dąbrowski-Tumański, Paweł; Niemyska, Wanda; Pasznik, Paweł; Sułkowska, Joanna I.

doi:10.1093/nar/gkw308

Cited by 58 publications

(68 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally we note, that based on the tools described in this paper, a systematic review of the whole PDB has already been conducted and all identified proteins with lasso motifs (including those presented in this paper) are deposited in the LassoProt database44. We are convinced that analysis of all those structures and their lasso motifs deserves further thorough studies.…”

Section: Discussionmentioning

confidence: 82%

Complex lasso: new entangled motifs in proteins

Niemyska

Dąbrowski-Tumański

Kadlof

et al. 2016

Sci Rep

Self Cite

108

View full text Add to dashboard Cite

We identify new entangled motifs in proteins that we call complex lassos. Lassos arise in proteins with disulfide bridges (or in proteins with amide linkages), when termini of a protein backbone pierce through an auxiliary surface of minimal area, spanned on a covalent loop. We find that as much as 18% of all proteins with disulfide bridges in a non-redundant subset of PDB form complex lassos, and classify them into six distinct geometric classes, one of which resembles supercoiling known from DNA. Based on biological classification of proteins we find that lassos are much more common in viruses, plants and fungi than in other kingdoms of life. We also discuss how changes in the oxidation/reduction potential may affect the function of proteins with lassos. Lassos and associated surfaces of minimal area provide new, interesting and possessing many potential applications geometric characteristics not only of proteins, but also of other biomolecules.

show abstract

Section: Discussionmentioning

confidence: 82%

Complex lasso: new entangled motifs in proteins

Niemyska

Dąbrowski-Tumański

Kadlof

et al. 2016

Sci Rep

Self Cite

108

View full text Add to dashboard Cite

show abstract

“…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%

“…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.…”

mentioning

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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Topological knots and links in proteins

Dąbrowski-Tumański

Sułkowska

2017

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

Self Cite

116

100

View full text Add to dashboard Cite

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...

show abstract

“…7, 8 In addition to these knotted systems in which the entanglements are formed solely by the protein backbone, other knot-like proteins and peptides are established via covalent sidechain-sidechain or sidechain-backbone crosslinks. A protein example of this type of entangled structure is the cytokine leptin 9 which exhibits a “pierced lasso” architecture 10, 11 formed by a disulfide bond. A well-studied example of knotting caused by disulfide bonding is the cystine knot motif, which occurs both in peptides 12 and in larger proteins.…”

Section: Introductionmentioning

confidence: 99%

Thermal Unthreading of the Lasso Peptides Astexin-2 and Astexin-3

et al. 2016

View full text Add to dashboard Cite

Lasso peptides are a class of knot-like polypeptides in which the C-terminal tail of the peptide threads through a ring formed by an isopeptide bond between the N-terminal amine group and a sidechain carboxylic acid. The small size (~20 amino acids) and simple topology of lasso peptides make them a good model system for studying the unthreading of entangled polypeptides, both with experiments and atomistic simulation. Here we present an in-depth study of the thermal unthreading behavior of two lasso peptides astexin-2 and astexin-3. Quantitative kinetics and energetics of the unthreading process were determined for variants of these peptides using a series of chromatography and mass spectrometry experiments and biased molecular dynamics (MD) simulations. In addition, we show that the Tyr15Phe variant of astexin-3 unthreads via an unprecedented “tail pulling” mechanism. MD simulations on a model ring-thread system coupled with machine learning approaches also led to the discovery of physicochemical descriptors most important for peptide unthreading.

show abstract

LassoProt: server to analyze biopolymers with lassos

Cited by 58 publications

References 29 publications

Complex lasso: new entangled motifs in proteins

Complex lasso: new entangled motifs in proteins

Topological knots and links in proteins

Thermal Unthreading of the Lasso Peptides Astexin-2 and Astexin-3

Contact Info

Product

Resources

About