RESUMO
Complex lasso proteins are a recently identified class of biological compounds that are present in considerable fraction of proteins with disulfide bridges. In this work, we look at complex lasso proteins as a generalization of well-known cysteine knots and miniproteins (lasso peptides). In particular, we show that complex lasso proteins with the same crucial topological features-cysteine knots and lasso peptides-are antimicrobial proteins, which suggests that they act as a molecular plug. Based on an analysis of the stability of the lasso piercing residue, we also introduce a method to determine which lasso motif is potentially functional. Using this method, we show that the lasso motif in antimicrobial proteins, as well in that in cytokines, is functionally relevant. We also study the evolution of lasso motifs, their conservation, and the usefulness of the lasso fingerprint, which extracts all topologically non-triviality concerning covalent loops. The work is completed by the presentation of extensive statistics on complex lasso proteins to analyze, in particular, the strange propensity for "negative" piercings. We also identify 21 previously unknown complex lasso proteins with an ester and a thioester bridge.
RESUMO
The increasing role of topology in (bio)physical properties of matter creates a need for an efficient method of detecting the topology of a (bio)polymer. However, the existing tools allow one to classify only the simplest knots and cannot be used in automated sample analysis. To answer this need, we created the Topoly Python package. This package enables the distinguishing of knots, slipknots, links and spatial graphs through the calculation of different topological polynomial invariants. It also enables one to create the minimal spanning surface on a given loop, e.g. to detect a lasso motif or to generate random closed polymers. It is capable of reading various file formats, including PDB. The extensive documentation along with test cases and the simplicity of the Python programming language make it a very simple to use yet powerful tool, suitable even for inexperienced users. Topoly can be obtained from https://topoly.cent.uw.edu.pl.
Assuntos
Algoritmos , Biologia Computacional/métodos , Conformação Molecular , Polímeros/química , Linguagens de Programação , Software , Gráficos por Computador , Simulação por Computador , Internet , Reprodutibilidade dos TestesRESUMO
Around 6% of protein structures deposited in the PDB are entangled, forming knots, slipknots, lassos, links, and θ-curves. In each of these cases, the protein backbone weaves through itself in a complex way, and at some point passes through a closed loop, formed by other regions of the protein structure. Such a passing can be interpreted as crossing a topological barrier. How proteins overcome such barriers, and therefore different degrees of frustration, challenged scientists and has shed new light on the field of protein folding. In this review, we summarize the current knowledge about the free energy landscape of proteins with non-trivial topology. We describe identified mechanisms which lead proteins to self-tying. We discuss the influence of excluded volume, such as crowding and chaperones, on tying, based on available data. We briefly discuss the diversity of topological complexity of proteins and their evolution. We also list available tools to investigate non-trivial topology. Finally, we formulate intriguing and challenging questions at the boundary of biophysics, bioinformatics, biology, and mathematics, which arise from the discovery of entangled proteins.