In this paper we show that a structure such as the Pierced Lasso Bundle, or a lasso in mini-proteins, is just a special case of a much more general and fascinating class of entangled “complex lasso” structures. Today more than 20 such proteins are known refs 14, 15, 16, 17, 18, 19. The peptide inhibits bacterial transcription by binding within, and obstructing, the nucleotide uptake channel of bacterial RNA polymerase. Its lasso structure was established 11 years later along with a description of its action 13. The first lasso structure was identified in 1994 11, however the first lasso peptide was the antibacterial peptide microcin J25 (MccJ25) 12 isolated in 1992.
In this case a loop is closed by amide linkage and typically it has a size of around 10 amino acids, similarly as the segment threading this loop. We note that structures with a similar geometric shape, called a lasso, were identified also in mini-proteins (also called lasso peptides). This structure is characterized by a part of a protein backbone being threaded through a loop comprised of a part of the chain closed by a disulfide bond. 10, where it was referred to as a Pierced Lasso Bundle. One simple example of a pierced lasso in a protein with a disulfide bond has been recently reported in ref. It is interesting to check if those proteins can fold according to the classical concept of the funnel landscape theory 9, with cysteine bridges created in the denatured state.
#Lasso server free#
In particular proteins with lassos constitute a new class of proteins with the topological barrier in the free energy landscape. Namely, we show that the presence of cysteine bridges results in very non-trivial topological configurations of the entire backbone chain that we call “lassos”, which are of biological, chemical, and mathematical interest. In this work we show that the presence of cysteine bridges has also very interesting consequences for the global structure of proteins. While cysteine bridges in general provide overall stability to proteins (for example in keratin 6), conformational changes due to reduction or oxidation of these bonds may allow proteins to change between different functions 7, 8.Īll the properties listed above are local, in the sense that they are related to the behavior of cysteine bridges or parts of a protein chain in the neighborhood of such bridges. For example in enzymes such as thioredoxin, cysteine bonds act as a cellular redox sensor via the oxidation status of thiol groups 5.
It is well known that the existence of cysteine bonds is important for structure, function, and stability of proteins.
We stress that lassos should not be confused with well known proteins with cysteine knots 4, which require 3 disulfide bridges (two building the covalent loop, and the third one piercing it). In this work we describe a new class of entangled structures that we call complex “lassos”, which arise in proteins with cysteine bridges. Their properties are currently very actively studied from various experimental and theoretical perspectives. While for a long time it had been suspected that it is very hard to create such structures, currently more than 1000 entangled proteins are known 1, some of them possessing quite complex knots (containing up to 6 crossings) 2, 3. Two classes of entangled structures have been analyzed in detail to date: proteins with knots and slipknots. In recent years entangled proteins attracted a lot of attention and a new field of research, devoted to their studies, emerged at the interface of biophysics, chemistry, and mathematical fields of topology and knot theory.
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