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1.
Molecules ; 28(22)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38005184

RESUMO

AlphaFold is a groundbreaking deep learning tool for protein structure prediction. It achieved remarkable accuracy in modeling many 3D structures while taking as the user input only the known amino acid sequence of proteins in question. Intriguingly though, in the early steps of each individual structure prediction procedure, AlphaFold does not respect topological barriers that, in real proteins, result from the reciprocal impermeability of polypeptide chains. This study aims to investigate how this failure to respect topological barriers affects AlphaFold predictions with respect to the topology of protein chains. We focus on such classes of proteins that, during their natural folding, reproducibly form the same knot type on their linear polypeptide chain, as revealed by their crystallographic analysis. We use partially artificial test constructs in which the mutual non-permeability of polypeptide chains should not permit the formation of complex composite knots during natural protein folding. We find that despite the formal impossibility that the protein folding process could produce such knots, AlphaFold predicts these proteins to form complex composite knots. Our study underscores the necessity for cautious interpretation and further validation of topological features in protein structures predicted by AlphaFold.


Assuntos
Dobramento de Proteína , Proteínas , Conformação Proteica , Modelos Moleculares , Proteínas/química , Peptídeos
2.
Nucleic Acids Res ; 47(2): 521-532, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30395328

RESUMO

Topologically associating domains (TADs) are megabase-sized building blocks of interphase chromosomes in higher eukaryotes. TADs are chromosomal regions with increased frequency of internal interactions. On average a pair of loci separated by a given genomic distance contact each other 2-3 times more frequently when they are in the same TAD as compared to a pair of loci located in two neighbouring TADs. TADs are also functional blocks of chromosomes as enhancers and their cognate promoters are normally located in the same TAD, even if their genomic distance from each other can be as large as a megabase. The internal structure of TADs, causing their increased frequency of internal interactions, is not established yet. We survey here experimental studies investigating presence of supercoiling in interphase chromosomes. We also review numerical simulation studies testing whether transcription-induced supercoiling of chromatin fibres can explain how TADs are formed and how they can assure very efficient interactions between enhancers and their cognate promoters located in the same TAD.


Assuntos
Cromossomos/química , DNA Super-Helicoidal , Cromatina , Elementos Facilitadores Genéticos , Modelos Genéticos , Regiões Promotoras Genéticas , Transcrição Gênica
3.
Nucleic Acids Res ; 47(14): 7182-7198, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31276584

RESUMO

Due to helical structure of DNA, massive amounts of positive supercoils are constantly introduced ahead of each replication fork. Positive supercoiling inhibits progression of replication forks but various mechanisms evolved that permit very efficient relaxation of that positive supercoiling. Some of these mechanisms lead to interesting topological situations where DNA supercoiling, catenation and knotting coexist and influence each other in DNA molecules being replicated. Here, we first review fundamental aspects of DNA supercoiling, catenation and knotting when these qualitatively different topological states do not coexist in the same circular DNA but also when they are present at the same time in replicating DNA molecules. We also review differences between eukaryotic and prokaryotic cellular strategies that permit relaxation of positive supercoiling arising ahead of the replication forks. We end our review by discussing very recent studies giving a long-sought answer to the question of how slow DNA topoisomerases capable of relaxing just a few positive supercoils per second can counteract the introduction of hundreds of positive supercoils per second ahead of advancing replication forks.


Assuntos
Replicação do DNA , DNA Catenado/química , DNA Circular/química , DNA Super-Helicoidal/química , DNA/química , Conformação de Ácido Nucleico , DNA/genética , Células Eucarióticas/metabolismo , Modelos Moleculares , Células Procarióticas/metabolismo
4.
Nucleic Acids Res ; 47(D1): D367-D375, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30508159

RESUMO

The KnotProt 2.0 database (the updated version of the KnotProt database) collects information about proteins which form knots and other entangled structures. New features in KnotProt 2.0 include the characterization of both probabilistic and deterministic entanglements which can be formed by disulfide bonds and interactions via ions, a refined characterization of entanglement in terms of knotoids, the identification of the so-called cysteine knots, the possibility to analyze all or a non-redundant set of proteins, and various technical updates. The KnotProt 2.0 database classifies all entangled proteins, represents their complexity in the form of a knotting fingerprint, and presents many biological and geometrical statistics based on these results. Currently the database contains >2000 entangled structures, and it regularly self-updates based on proteins deposited in the Protein Data Bank (PDB).


Assuntos
Bases de Dados de Proteínas , Modelos Moleculares , Conformação Proteica , Algoritmos , Animais , Cisteína/química , Cistina/química , Gerenciamento de Dados , Humanos , Íons/química , Probabilidade , Dobramento de Proteína , Interface Usuário-Computador
5.
Biophys J ; 118(9): 2268-2279, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-31818464

RESUMO

Knots in the human genome would greatly impact diverse cellular processes ranging from transcription to gene regulation. To date, it has not been possible to directly examine the genome in vivo for the presence of knots. Recently, methods for serial fluorescent in situ hybridization have made it possible to measure the three-dimensional position of dozens of consecutive genomic loci in vivo. However, the determination of whether genomic trajectories are knotted remains challenging because small errors in the localization of a single locus can transform an unknotted trajectory into a highly knotted trajectory and vice versa. Here, we use stochastic closure analysis to determine if a genomic trajectory is knotted in the setting of experimental noise. We analyze 4727 deposited genomic trajectories of a 2-Mb-long chromatin interval from human chromosome 21. For 243 of these trajectories, their knottedness could be reliably determined despite the possibility of localization errors. Strikingly, in each of these 243 cases, the trajectory was unknotted. We note a potential source of bias insofar as knotted contours may be more difficult to reliably resolve. Nevertheless, our data are consistent with a model in which, at the scales probed, the human genome is often free of knots.


Assuntos
Cromatina , Cromatina/genética , Humanos , Hibridização in Situ Fluorescente , Modelos Moleculares
6.
Nucleic Acids Res ; 46(17): 9181-9188, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-29982678

RESUMO

During DNA replication in living cells some DNA knots are inadvertently produced by DNA topoisomerases facilitating progression of replication forks. The types of DNA knots formed are conditioned by the 3D organization of replicating DNA molecules. Therefore, by characterizing formed DNA knots it is possible to infer the 3D arrangement of replicating DNA molecules. This topological inference method is highly developed for knotted DNA circles. However, partially replicated DNA molecules have the form of θ-curves. In this article, we use mathematical formalism of θ-curves to characterize the full possibilities of how knotting can occur during replication of DNA molecules in vivo. To do this, we reanalyze earlier experimental studies of knotted, partially replicated DNA molecules and the previously proposed pathway of their formation. We propose a general model of knotting in replication intermediates, and demonstrate that there is an additional, equally important, parallel knotting pathway that also explains how DNA topoisomerases can produce experimentally observed knotted θ-curves. Interestingly, both pathways require intertwining of freshly replicated sister duplexes (precatenanes).


Assuntos
Replicação do DNA/fisiologia , DNA Circular/metabolismo , DNA Super-Helicoidal/química , Conformação de Ácido Nucleico , DNA Topoisomerase IV/metabolismo , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , DNA Circular/química , DNA Circular/genética , DNA Super-Helicoidal/genética , Escherichia coli/genética , Origem de Replicação/genética , Estereoisomerismo
7.
Nucleic Acids Res ; 46(4): 1648-1660, 2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29140466

RESUMO

Using molecular dynamics simulations, we show here that growing plectonemes resulting from transcription-induced supercoiling have the ability to actively push cohesin rings along chromatin fibres. The pushing direction is such that within each topologically associating domain (TAD) cohesin rings forming handcuffs move from the source of supercoiling, constituted by RNA polymerase with associated DNA topoisomerase TOP1, towards borders of TADs, where supercoiling is released by topoisomerase TOPIIB. Cohesin handcuffs are pushed by continuous flux of supercoiling that is generated by transcription and is then progressively released by action of TOPIIB located at TADs borders. Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites. We discuss the role of supercoiling in stimulating enhancer promoter contacts and propose that transcription of eRNA sends the first wave of supercoiling that can activate mRNA transcription in a given TAD.


Assuntos
Cromatina/química , DNA Super-Helicoidal/química , Transcrição Gênica , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/química , Interfase/genética , Modelos Genéticos , Simulação de Dinâmica Molecular , Rotação , Coesinas
8.
Bioinformatics ; 34(19): 3402-3404, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29722808

RESUMO

Summary: The backbone of most proteins forms an open curve. To study their entanglement, a common strategy consists in searching for the presence of knots in their backbones using topological invariants. However, this approach requires to close the curve into a loop, which alters the geometry of curve. Knoto-ID allows evaluating the entanglement of open curves without the need to close them, using the recent concept of knotoids which is a generalization of the classical knot theory to open curves. Knoto-ID can analyse the global topology of the full chain as well as the local topology by exhaustively studying all subchains or only determining the knotted core. Knoto-ID permits to localize topologically non-trivial protein folds that are not detected by informatics tools detecting knotted protein folds. Availability and implementation: Knoto-ID is written in C++ and includes R (www.R-project.org) scripts to generate plots of projections maps, fingerprint matrices and disk matrices. Knoto-ID is distributed under the GNU General Public License (GPL), version 2 or any later version and is available at https://github.com/sib-swiss/Knoto-ID. A binary distribution for Mac OS X, Linux and Windows with detailed user guide and examples can be obtained from https://www.vital-it.ch/software/Knoto-ID.


Assuntos
Conformação Proteica , Proteínas/química , Software , Biologia Computacional
9.
Nucleic Acids Res ; 45(17): 9850-9859, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-28973473

RESUMO

The question of how self-interacting chromatin domains in interphase chromosomes are structured and generated dominates current discussions on eukaryotic chromosomes. Numerical simulations using standard polymer models have been helpful in testing the validity of various models of chromosome organization. Experimental contact maps can be compared with simulated contact maps and thus verify how good is the model. With increasing resolution of experimental contact maps, it became apparent though that active processes need to be introduced into models to recapitulate the experimental data. Since transcribing RNA polymerases are very strong molecular motors that induce axial rotation of transcribed DNA, we present here models that include such rotational motors. We also include into our models swivels and sites for intersegmental passages that account for action of DNA topoisomerases releasing torsional stress. Using these elements in our models, we show that transcription-induced supercoiling generated in the regions with divergent-transcription and supercoiling relaxation occurring between these regions are sufficient to explain formation of self-interacting chromatin domains in chromosomes of fission yeast (S. pombe).


Assuntos
DNA Topoisomerases/química , DNA Fúngico/química , DNA Super-Helicoidal/química , RNA Polimerases Dirigidas por DNA/química , Schizosaccharomyces/genética , Transcrição Gênica , Fenômenos Biomecânicos , Cromatina/química , Cromatina/metabolismo , Cromossomos Fúngicos/química , Cromossomos Fúngicos/metabolismo , DNA Topoisomerases/genética , DNA Topoisomerases/metabolismo , DNA Fúngico/genética , DNA Fúngico/metabolismo , DNA Super-Helicoidal/genética , DNA Super-Helicoidal/metabolismo , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Regulação Fúngica da Expressão Gênica , Simulação de Dinâmica Molecular , Rotação , Schizosaccharomyces/metabolismo
10.
Phys Rev Lett ; 121(12): 127801, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30296142

RESUMO

We study the dynamics of knotted deformable closed chains sedimenting in a viscous fluid. We show experimentally that trefoil and other torus knots often attain a remarkably regular horizontal toroidal structure while sedimenting, with a number of intertwined loops, oscillating periodically around each other. We then recover this motion numerically and find out that it is accompanied by a very slow rotation around the vertical symmetry axis. We analyze the dependence of the characteristic timescales on the chain flexibility and aspect ratio. It is observed in the experiments that this oscillating mode of the dynamics can spontaneously form even when starting from a qualitatively different initial configuration. In numerical simulations, the oscillating modes are usually present as transients or final stages of the evolution, depending on chain aspect ratio and flexibility, and the number of loops.

11.
Mol Cell ; 37(6): 865-78, 2010 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-20347428

RESUMO

FANCM remodels branched DNA structures and plays essential roles in the cellular response to DNA replication stress. Here, we show that FANCM forms a conserved DNA-remodeling complex with a histone-fold heterodimer, MHF. We find that MHF stimulates DNA binding and replication fork remodeling by FANCM. In the cell, FANCM and MHF are rapidly recruited to forks stalled by DNA interstrand crosslinks, and both are required for cellular resistance to such lesions. In vertebrates, FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage, and suppresses sister-chromatid exchanges. Yeast orthologs of these proteins function together to resist MMS-induced DNA damage and promote gene conversion at blocked replication forks. Thus, FANCM-MHF is an essential DNA-remodeling complex that protects replication forks from yeast to human.


Assuntos
DNA Helicases/metabolismo , DNA/metabolismo , Instabilidade Genômica , Histonas/metabolismo , Dobramento de Proteína , Multimerização Proteica , Sequência de Aminoácidos , Animais , Linhagem Celular , Galinhas , DNA/genética , Dano ao DNA , DNA Helicases/química , DNA Helicases/genética , Replicação do DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Evolução Molecular , Proteínas de Grupos de Complementação da Anemia de Fanconi , Humanos , Dados de Sequência Molecular , Ligação Proteica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Alinhamento de Sequência , Troca de Cromátide Irmã
12.
Nucleic Acids Res ; 44(10): 4528-38, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27106058

RESUMO

Freshly replicated DNA molecules initially form multiply interlinked right-handed catenanes. In bacteria, these catenated molecules become supercoiled by DNA gyrase before they undergo a complete decatenation by topoisomerase IV (Topo IV). Topo IV is also involved in the unknotting of supercoiled DNA molecules. Using Metropolis Monte Carlo simulations, we investigate the shapes of supercoiled DNA molecules that are either knotted or catenated. We are especially interested in understanding how Topo IV can unknot right-handed knots and decatenate right-handed catenanes without acting on right-handed plectonemes in negatively supercoiled DNA molecules. To this end, we investigate how the topological consequences of intersegmental passages depend on the geometry of the DNA-DNA juxtapositions at which these passages occur. We observe that there are interesting differences between the geometries of DNA-DNA juxtapositions in the interwound portions and in the knotted or catenated portions of the studied molecules. In particular, in negatively supercoiled, multiply interlinked, right-handed catenanes, we detect specific regions where DNA segments belonging to two freshly replicated sister DNA molecules form left-handed crossings. We propose that, due to its geometrical preference to act on left-handed crossings, Topo IV can specifically unknot supercoiled DNA, as well as decatenate postreplicative catenanes, without causing their torsional relaxation.


Assuntos
DNA Topoisomerase IV/química , DNA Topoisomerase IV/metabolismo , DNA/química , DNA/metabolismo , Modelos Moleculares , Método de Monte Carlo , Conformação de Ácido Nucleico
13.
Nucleic Acids Res ; 43(15): 7229-36, 2015 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-26150424

RESUMO

Due to the helical structure of DNA the process of DNA replication is topologically complex. Freshly replicated DNA molecules are catenated with each other and are frequently knotted. For proper functioning of DNA it is necessary to remove all of these entanglements. This is done by DNA topoisomerases that pass DNA segments through each other. However, it has been a riddle how DNA topoisomerases select the sites of their action. In highly crowded DNA in living cells random passages between contacting segments would only increase the extent of entanglement. Using molecular dynamics simulations we observed that in actively supercoiled DNA molecules the entanglements resulting from DNA knotting or catenation spontaneously approach sites of nicks and gaps in the DNA. Type I topoisomerases, that preferentially act at sites of nick and gaps, are thus naturally provided with DNA-DNA juxtapositions where a passage results in an error-free DNA unknotting or DNA decatenation.


Assuntos
DNA Catenado/química , DNA Super-Helicoidal/química , DNA/química , Replicação do DNA , DNA Topoisomerases Tipo I/metabolismo , DNA Catenado/metabolismo , DNA Circular/química , DNA Super-Helicoidal/metabolismo , Simulação de Dinâmica Molecular
14.
Nucleic Acids Res ; 43(Database issue): D306-14, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25361973

RESUMO

The protein topology database KnotProt, http://knotprot.cent.uw.edu.pl/, collects information about protein structures with open polypeptide chains forming knots or slipknots. The knotting complexity of the cataloged proteins is presented in the form of a matrix diagram that shows users the knot type of the entire polypeptide chain and of each of its subchains. The pattern visible in the matrix gives the knotting fingerprint of a given protein and permits users to determine, for example, the minimal length of the knotted regions (knot's core size) or the depth of a knot, i.e. how many amino acids can be removed from either end of the cataloged protein structure before converting it from a knot to a different type of knot. In addition, the database presents extensive information about the biological functions, families and fold types of proteins with non-trivial knotting. As an additional feature, the KnotProt database enables users to submit protein or polymer chains and generate their knotting fingerprints.


Assuntos
Bases de Dados de Proteínas , Conformação Proteica , Peptídeos/química
15.
Nucleic Acids Res ; 43(4): 2390-9, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25653164

RESUMO

DNA in bacterial chromosomes and bacterial plasmids is supercoiled. DNA supercoiling is essential for DNA replication and gene regulation. However, the density of supercoiling in vivo is circa twice smaller than in deproteinized DNA molecules isolated from bacteria. What are then the specific advantages of reduced supercoiling density that is maintained in vivo? Using Brownian dynamics simulations and atomic force microscopy we show here that thanks to physiological DNA-DNA crowding DNA molecules with reduced supercoiling density are still sufficiently supercoiled to stimulate interaction between cis-regulatory elements. On the other hand, weak supercoiling permits DNA molecules to modulate their overall shape in response to physiological changes in DNA crowding. This plasticity of DNA shapes may have regulatory role and be important for the postreplicative spontaneous segregation of bacterial chromosomes.


Assuntos
DNA Super-Helicoidal/química , DNA/química , DNA/ultraestrutura , DNA Circular/química , Elementos Facilitadores Genéticos , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Regiões Promotoras Genéticas
16.
Nucleic Acids Res ; 43(4): e24, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25414338

RESUMO

We systematically varied conditions of two-dimensional (2D) agarose gel electrophoresis to optimize separation of DNA topoisomers that differ either by the extent of knotting, the extent of catenation or the extent of supercoiling. To this aim we compared electrophoretic behavior of three different families of DNA topoisomers: (i) supercoiled DNA molecules, where supercoiling covered the range extending from covalently closed relaxed up to naturally supercoiled DNA molecules; (ii) postreplicative catenanes with catenation number increasing from 1 to ∼15, where both catenated rings were nicked; (iii) knotted but nicked DNA molecules with a naturally arising spectrum of knots. For better comparison, we studied topoisomer families where each member had the same total molecular mass. For knotted and supercoiled molecules, we analyzed dimeric plasmids whereas catenanes were composed of monomeric forms of the same plasmid. We observed that catenated, knotted and supercoiled families of topoisomers showed different reactions to changes of agarose concentration and voltage during electrophoresis. These differences permitted us to optimize conditions for their separation and shed light on physical characteristics of these different types of DNA topoisomers during electrophoresis.


Assuntos
DNA Catenado/química , DNA Super-Helicoidal/química , DNA/química , Eletroforese em Gel de Ágar/métodos , Eletroforese em Gel Bidimensional/métodos , DNA/isolamento & purificação , DNA Catenado/isolamento & purificação , DNA Super-Helicoidal/isolamento & purificação , Conformação de Ácido Nucleico
17.
Nucleic Acids Res ; 42(16): 10425-32, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25123662

RESUMO

Using Brownian dynamics simulations, we investigate here one of possible roles of supercoiling within topological domains constituting interphase chromosomes of higher eukaryotes. We analysed how supercoiling affects the interaction between enhancers and promoters that are located in the same or in neighbouring topological domains. We show here that enhancer-promoter affinity and supercoiling act synergistically in increasing the fraction of time during which enhancer and promoter stay in contact. This stabilizing effect of supercoiling only acts on enhancers and promoters located in the same topological domain. We propose that the primary role of recently observed supercoiling of topological domains in interphase chromosomes of higher eukaryotes is to assure that enhancers contact almost exclusively their cognate promoters located in the same topological domain and avoid contacts with very similar promoters but located in neighbouring topological domains.


Assuntos
DNA Super-Helicoidal/metabolismo , Elementos Facilitadores Genéticos , Regiões Promotoras Genéticas , Simulação de Dinâmica Molecular
18.
Nucleic Acids Res ; 42(5): 2848-55, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24366878

RESUMO

Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.


Assuntos
Cromatina/química , Cromossomos/química , Interfase/genética , Modelos Moleculares , Simulação por Computador , DNA Super-Helicoidal/química
19.
Nucleic Acids Res ; 41(14): 6808-15, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23742906

RESUMO

Using numerical simulations of pairs of long polymeric chains confined in microscopic cylinders, we investigate consequences of double-strand DNA breaks occurring in independent topological domains, such as these constituting bacterial chromosomes. Our simulations show a transition between segregated and mixed state upon linearization of one of the modelled topological domains. Our results explain how chromosomal organization into topological domains can fulfil two opposite conditions: (i) effectively repulse various loops from each other thus promoting chromosome separation and (ii) permit local DNA intermingling when one or more loops are broken and need to be repaired in a process that requires homology search between broken ends and their homologous sequences in closely positioned sister chromatid.


Assuntos
Cromossomos Bacterianos/química , Quebras de DNA de Cadeia Dupla , Modelos Moleculares , Método de Monte Carlo
20.
Proc Natl Acad Sci U S A ; 109(26): E1715-23, 2012 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-22685208

RESUMO

While analyzing all available protein structures for the presence of knots and slipknots, we detected a strict conservation of complex knotting patterns within and between several protein families despite their large sequence divergence. Because protein folding pathways leading to knotted native protein structures are slower and less efficient than those leading to unknotted proteins with similar size and sequence, the strict conservation of the knotting patterns indicates an important physiological role of knots and slipknots in these proteins. Although little is known about the functional role of knots, recent studies have demonstrated a protein-stabilizing ability of knots and slipknots. Some of the conserved knotting patterns occur in proteins forming transmembrane channels where the slipknot loop seems to strap together the transmembrane helices forming the channel.


Assuntos
Proteínas/química , Conformação Proteica , Dobramento de Proteína
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