Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dual Self-Assembled Nanostructures from Intrinsically Disordered Protein Polymers with LCST Behavior and Antimicrobial Peptides.

ABSTRACT: Antimicrobial peptides (AMPs) have attracted great interest as they constitute one of the most promising alternatives against drug-resistant infections. Their amphipathic nature not only provides them antimicrobial and immunomodulatory properties but also the ability to self-assemble into supramolecular nanostructures. Here, we propose their use as self-assembling domains to drive hierarchical organization of intrinsically disordered protein polymers (IDPPs). Using a modular approach, hybrid protein-engineered polymers were recombinantly produced, thus combining designer AMPs and a thermoresponsive IDPP, an elastin-like recombinamer (ELR). We exploited the ability of these AMPs and ELRs to self-assemble to develop supramolecular nanomaterials by way of a dual-assembly process. First, the AMPs trigger the formation of nanofibers; then, the thermoresponsiveness of the ELRs enables assembly into fibrillar aggregates. The interplay between the assembly of AMPs and ELRs provides an innovative molecular tool in the development of self-assembling nanosystems with potential use for biotechnological and biomedical applications.

SUBMITTER: Acosta S

PROVIDER: S-EPMC7558458 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Regulation and aggregation of intrinsically disordered peptides.

Project description:Intrinsically disordered proteins (IDPs) are a unique class of proteins that have no stable native structure, a feature that allows them to adopt a wide variety of extended and compact conformations that facilitate a large number of vital physiological functions. One of the most well-known IDPs is the microtubule-associated tau protein, which regulates microtubule growth in the nervous system. However, dysfunctions in tau can lead to tau oligomerization, fibril formation, and neurodegenerative disease, including Alzheimer's disease. Using a combination of simulations and experiments, we explore the role of osmolytes in regulating the conformation and aggregation propensities of the R2/wt peptide, a fragment of tau containing the aggregating paired helical filament (PHF6*). We show that the osmolytes urea and trimethylamine N-oxide (TMAO) shift the population of IDP monomer structures, but that no new conformational ensembles emerge. Although urea halts aggregation, TMAO promotes the formation of compact oligomers (including helical oligomers) through a newly proposed mechanism of redistribution of water around the perimeter of the peptide. We put forth a "superposition of ensembles" hypothesis to rationalize the mechanism by which IDP structure and aggregation is regulated in the cell.

| S-EPMC4352815 | biostudies-other

Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers.

Project description:Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level.

| S-EPMC4618764 | biostudies-literature

Comparison of structure determination methods for intrinsically disordered amyloid-? peptides.

Project description:Intrinsically disordered proteins (IDPs) represent a new frontier in structural biology since the primary characteristic of IDPs is that structures need to be characterized as diverse ensembles of conformational substates. We compare two general but very different ways of combining NMR spectroscopy with theoretical methods to derive structural ensembles for the disease IDPs amyloid-? 1-40 and amyloid-? 1-42, which are associated with Alzheimer's Disease. We analyze the performance of de novo molecular dynamics and knowledge-based approaches for generating structural ensembles by assessing their ability to reproduce a range of NMR experimental observables. In addition to the comparison of computational methods, we also evaluate the relative value of different types of NMR data for refining or validating the IDP structural ensembles for these important disease peptides.

| S-EPMC4066902 | biostudies-literature

An intrinsically disordered antimicrobial peptide dendrimer from stereorandomized virtual screening.

Project description:Membrane-disruptive amphiphilic antimicrobial peptides behave as intrinsically disordered proteins by being unordered in water and becoming α-helical in contact with biological membranes. We recently discovered that synthesizing the α-helical antimicrobial peptide dendrimer L-T25 ((KL)8(KKL)4(KLL)2 KKLL) using racemic amino acids to form stereorandomized sr-T25, an analytically pure mixture of all possible diastereoisomers of L-T25, preserved antibacterial activity but abolished hemolysis and cytotoxicity, pointing to an intrinsically disordered antibacterial conformation and an α-helical cytotoxic conformation. In this study, to identify non-toxic intrinsically disordered homochiral antimicrobial peptide dendrimers (AMPDs), we surveyed sixty-three sr-analogs of sr-T25 selected by virtual screening. One of the analogs, sr-X18 ((KL)8(KLK)4(KLL)2 KLLL), lost antibacterial activity as L-enantiomer and became hemolytic due to α-helical folding. By contrast, the L- and D-enantiomers of sr-X22 ((KL)8(KL)4(KKLL)2 KLKK) were equally antibacterial, non-hemolytic, and non-toxic, implying an intrinsically disordered bioactive conformation. Screening stereorandomized libraries may be generally useful to identify or optimize intrinsically disordered bioactive peptides.

| S-EPMC9780108 | biostudies-literature

Cationic Intrinsically Disordered Antimicrobial Peptides (CIDAMPs) Represent a New Paradigm of Innate Defense with a Potential for Novel Anti-Infectives.

Project description:In the search for potential mechanisms underlying the remarkable resistance of healthy skin against infection by soil bacteria like Pseudomonas (P.) aeruginosa we identified fragments of the intrinsically disordered protein hornerin as potent microbicidal agents in the stratum corneum. We found that, independent of the amino acid (AA)-sequence, any tested linear cationic peptide containing a high percentage of disorder-promoting AA and a low percentage of order-promoting AA is a potent microbicidal antimicrobial. We further show that the antimicrobial activity of these cationic intrinsically disordered antimicrobial peptides (CIDAMPs) depends on the peptide chain length, its net charge, lipidation and environmental conditions. The ubiquitous presence of latent CIDAMP sources in nature suggests a common and yet overlooked adapted innate disinfection system of body surfaces. The simple structure and virtually any imaginable sequence or composition of disorder-promoting AA allow the generation of a plethora of CIDAMPs. These are potential novel microbicidal anti-infectives for various bacterial pathogens, including P. aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA) and fungal pathogens like Candida albicans and Cryptococcus neoformans.

| S-EPMC6399351 | biostudies-literature

Folding and self-assembly of short intrinsically disordered peptides and protein regions.

Project description:Proteins and peptide fragments are highly relevant building blocks in self-assembly for nanostructures with plenty of applications. Intrinsically disordered proteins (IDPs) and protein regions (IDRs) are defined by the absence of a well-defined secondary structure, yet IDPs/IDRs show a significant biological activity. Experimental techniques and computational modelling procedures for the characterization of IDPs/IDRs are discussed. Directed self-assembly of IDPs/IDRs allows reaching a large variety of nanostructures. Hybrid materials based on the derivatives of IDPs/IDRs show a promising performance as alternative biocides and nanodrugs. Cell mimicking, in vivo compartmentalization, and bone regeneration are demonstrated for IDPs/IDRs in biotechnological applications. The exciting possibilities of IDPs/IDRs in nanotechnology with relevant biological applications are shown.

| S-EPMC9417027 | biostudies-literature

Phytopathogenic protist Albugo candida secretes cationic intrinsically disordered peptides with antimicrobial activity against plant-associated bacteria

Project description:Positive and negative ecological interactions shape the dynamics and composition of natural microbial communities. The mechanisms behind microbe-microbe interactions, particularly those protein-based, are not well understood and only a small percentage of such interactions has been studied. We hypothesize that secreted proteins are a powerful and highly specific toolset to shape and defend a favorable plant niche. Here, we have studied Albugo candida, an obligate plant parasite from the protist Oomycota phylum, for its potential to inhibit and promote the growth of bacteria through secretion of proteins into the apoplast. Amplicon sequencing and network analysis of Albugo-infected and uninfected samples revealed an abundance of negative correlations between Albugo and other phyllosphere microbes. Analysis of the secreted proteome of Albugo candida combined with machine-learning predictors enabled the selection of candidates for heterologous expression and study of their inhibitory activity in vitro. We found that three of the candidate proteins showed a selective antimicrobial activity on several gram-positive bacterial strains isolated from Arabidopsis thaliana. We could ascribe the antibacterial activity of the candidates to their intrinsically disordered regions and positively correlate it with their net charge. This is the first report of protist proteins that have an antimicrobial activity under apoplastic conditions and therefore are potential biocontrol tools for a targeted manipulation of the microbiome.

2023-05-31 | PXD031981 | Pride

Relation between single-molecule properties and phase behavior of intrinsically disordered proteins.

Project description:Proteins that undergo liquid-liquid phase separation (LLPS) have been shown to play a critical role in many physiological functions through formation of condensed liquid-like assemblies that function as membraneless organelles within biological systems. To understand how different proteins may contribute differently to these assemblies and their functions, it is important to understand the molecular driving forces of phase separation and characterize their phase boundaries and material properties. Experimental studies have shown that intrinsically disordered regions of these proteins are a major driving force, as many of them undergo LLPS in isolation. Previous work on polymer solution phase behavior suggests a potential correspondence between intramolecular and intermolecular interactions that can be leveraged to discover relationships between single-molecule properties and phase boundaries. Here, we take advantage of a recently developed coarse-grained framework to calculate the θ temperature [Formula: see text], the Boyle temperature [Formula: see text], and the critical temperature [Formula: see text] for 20 diverse protein sequences, and we show that these three properties are highly correlated. We also highlight that these correlations are not specific to our model or simulation methodology by comparing between different pairwise potentials and with data from other work. We, therefore, suggest that smaller simulations or experiments to determine [Formula: see text] or [Formula: see text] can provide useful insights into the corresponding phase behavior.

| S-EPMC6176625 | biostudies-literature

Effect of Osmolytes on Conformational Behavior of Intrinsically Disordered Protein α-Synuclein.

Project description:α-Synuclein is an intrinsically disordered protein whose function in a healthy brain is poorly understood. It is genetically and neuropathologically linked to Parkinson's disease (PD). PD is manifested after the accumulation of plaques of α-synuclein aggregates in the brain cells. Aggregates of α-synuclein are very toxic and lead to the disruption of cellular homeostasis and neuronal death. α-Synuclein can also contribute to disease propagation as it may exert noxious effects on neighboring cells. Understanding the mechanism of α-synuclein aggregation will facilitate the problem of dealing with neurodegenerative diseases in general and that of PD in particular. Here, we have used molecular dynamics simulations to investigate the behavior of α-synuclein at various temperatures and in different concentrations of urea and trimethyl amine oxide. The residue region from 61 to 95 of α-synuclein is experimentally known as amyloidogenic. In our study, we have identified some other regions, which also have the propensity to form an aggregate besides this known sequence. Urea being a denaturant interacts more with these regions of α-synuclein through hydrogen bond formation and inhibits the β-sheet formation, whereas trimethyl amine oxide itself does not interact much with the protein and stabilizes the protein by preferentially distributing water molecules on the surface of the protein.

| S-EPMC7031737 | biostudies-literature

A New Tool to Study the Binding Behavior of Intrinsically Disordered Proteins.

Project description:Understanding the binding behavior and conformational dynamics of intrinsically disordered proteins (IDPs) is crucial for unraveling their regulatory roles in biological processes. However, their lack of stable 3D structures poses challenges for analysis. To address this, we propose an algorithm that explores IDP binding behavior with protein complexes by extracting topological and geometric features from the protein surface model. Our algorithm identifies a geometrically favorable binding pose for the IDP and plans a feasible trajectory to evaluate its transition to the docking position. We focus on IDPs from Homo sapiens and Mus-musculus, investigating their interaction with the Plasmodium falciparum (PF) pathogen associated with malaria-related deaths. We compare our algorithm with HawkDock and HDOCK docking tools for quantitative (computation time) and qualitative (binding affinity) measures. Our results indicated that our method outperformed the compared methods in computation performance and binding affinity in experimental conformations.

| S-EPMC10380747 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data