Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Halogenation dictates the architecture of amyloid peptide nanostructures.

ABSTRACT: Amyloid peptides yield a plethora of interesting nanostructures though difficult to control. Here we report that depending on the number, position, and nature of the halogen atoms introduced into either one or both phenylalanine benzene rings of the amyloid ? peptide-derived core-sequence KLVFF, four different architectures were obtained in a controlled manner. Our findings demonstrate that halogenation may develop as a general strategy to engineer amyloidal peptide self-assembly and obtain new amyloidal nanostructures.

SUBMITTER: Pizzi A

PROVIDER: S-EPMC5708343 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Halogenation dictates the architecture of amyloid peptide nanostructures.

Pizzi Andrea A Pigliacelli Claudia C Gori Alessandro A Nonappa Ikkala Olli O Demitri Nicola N Terraneo Giancarlo G Castelletto Valeria V Hamley Ian W IW Baldelli Bombelli Francesca F Metrangolo Pierangelo P

Nanoscale 20170701 28

Amyloid peptides yield a plethora of interesting nanostructures though difficult to control. Here we report that depending on the number, position, and nature of the halogen atoms introduced into either one or both phenylalanine benzene rings of the amyloid β peptide-derived core-sequence KLVFF, four different architectures were obtained in a controlled manner. Our findings demonstrate that halogenation may develop as a general strategy to engineer amyloidal peptide self-assembly and obtain new ...[more]

PMID: 28696473

Similar Datasets

Amino acid sequence in constitutionally isomeric tetrapeptide amphiphiles dictates architecture of one-dimensional nanostructures.

Project description:The switching of two adjacent amino acids can lead to differences in how proteins fold thus affecting their function. This effect has not been extensively explored in synthetic peptides in the context of supramolecular self-assembly. Toward this end, we report here the use of isomeric peptide amphiphiles as molecular building blocks to create one-dimensional (1D) nanostructures. We show that four peptide amphiphile isomers, with identical composition but a different sequence of their four amino acids, can form drastically different types of 1D nanostructures under the same conditions. We found that molecules with a peptide sequence of alternating hydrophobic and hydrophilic amino acids such as VEVE and EVEV self-assemble into flat nanostructures that can be either helical or twisted. On the other hand, nonalternating isomers such as VVEE and EEVV result in the formation of cylindrical nanofibers. Furthermore, we also found that when the glutamic acid is adjacent to the alkyl tail the supramolecular assemblies appear to be internally flexible compared to those with valine as the first amino acid. These results clearly demonstrate the significance of peptide side chain interactions in determining the architectures of supramolecular assemblies.

| S-EPMC4156871 | biostudies-other

Halogenation generates effective modulators of amyloid-Beta aggregation and neurotoxicity.

Project description:Halogenation of organic compounds plays diverse roles in biochemistry, including selective chemical modification of proteins and improved oral absorption/blood-brain barrier permeability of drug candidates. Moreover, halogenation of aromatic molecules greatly affects aromatic interaction-mediated self-assembly processes, including amyloid fibril formation. Perturbation of the aromatic interaction caused by halogenation of peptide building blocks is known to affect the morphology and other physical properties of the fibrillar structure. Consequently, in this article, we investigated the ability of halogenated ligands to modulate the self-assembly of amyloidogenic peptide/protein. As a model system, we chose amyloid-beta peptide (A?), which is implicated in Alzheimer's disease, and a novel modulator of A? aggregation, erythrosine B (ERB). Considering that four halogen atoms are attached to the xanthene benzoate group in ERB, we hypothesized that halogenation of the xanthene benzoate plays a critical role in modulating A? aggregation and cytotoxicity. Therefore, we evaluated the modulating capacities of four ERB analogs containing different types and numbers of halogen atoms as well as fluorescein as a negative control. We found that fluorescein is not an effective modulator of A? aggregation and cytotoxicity. However, halogenation of either the xanthenes or benzoate ring of fluorescein substantially enhanced the inhibitory capacity on A? aggregation. Such A? aggregation inhibition by ERB analogs except rose bengal correlated well to the inhibition of A? cytotoxicity. To our knowledge, this is the first report demonstrating that halogenation of aromatic rings substantially enhance inhibitory capacities of small molecules on A?-associated neurotoxicity via A? aggregation modulation.

| S-EPMC3585355 | biostudies-literature

A peptide extension dictates IgM assembly.

Project description:Professional secretory cells can produce large amounts of high-quality complex molecules, including IgM antibodies. Owing to their multivalency, polymeric IgM antibodies provide an efficient first-line of defense against pathogens. To decipher the mechanisms of IgM assembly, we investigated its biosynthesis in living cells and faithfully reconstituted the underlying processes in vitro. We find that a conserved peptide extension at the C-terminal end of the IgM heavy (Ig-?) chains, termed the tailpiece, is necessary and sufficient to establish the correct geometry. Alanine scanning revealed that hydrophobic amino acids in the first half of the tailpiece contain essential information for generating the correct topology. Assembly is triggered by the formation of a disulfide bond linking two tailpieces. This induces conformational changes in the tailpiece and the adjacent domain, which drive further polymerization. Thus, the biogenesis of large and topologically challenging IgM complexes is dictated by a local conformational switch in a peptide extension.

| S-EPMC5642677 | biostudies-literature

Nanostructures Formed by Custom-Made Peptides Based on Amyloid Peptide Sequences and Their Inhibition by 2-Hydroxynaphthoquinone.

Project description:Extensive research on amyloid fibril formations shows that certain core sequences within Aβ peptide play an important role in their formation. It is impossible to track these events in vivo. Many proteins and peptides with such core sequences form amyloid fibrils and such Aβ sheet mimics have become excellent tools to study amyloid fibril formation and develop therapeutic strategies. A group of peptides based on amyloid peptide sequences obtained from PDB searches, where glycine residues are substituted with alanine and isoleucine, are tested for aggregation by SEM and ThT binding assay. SEM of different peptide sequences showed morphologically different structures such as nanorods, crystalline needles and nanofibrils. The peptides were co-incubated with HNQ (a quinone) to study its effect on the process of aggregation and/or fibrillation. In conclusion, this group of peptides seem to be Aβ sheet mimics and can be very useful in understanding the different morphologies of amyloid fibrils arising from different peptide sequences and the effective strategies to inhibit or anneal them.

| S-EPMC7424059 | biostudies-literature

Biocatalysts Based on Peptide and Peptide Conjugate Nanostructures.

Project description:Peptides and their conjugates (to lipids, bulky N-terminals, or other groups) can self-assemble into nanostructures such as fibrils, nanotubes, coiled coil bundles, and micelles, and these can be used as platforms to present functional residues in order to catalyze a diversity of reactions. Peptide structures can be used to template catalytic sites inspired by those present in natural enzymes as well as simpler constructs using individual catalytic amino acids, especially proline and histidine. The literature on the use of peptide (and peptide conjugate) α-helical and β-sheet structures as well as turn or disordered peptides in the biocatalysis of a range of organic reactions including hydrolysis and a variety of coupling reactions (e.g., aldol reactions) is reviewed. The simpler design rules for peptide structures compared to those of folded proteins permit ready ab initio design (minimalist approach) of effective catalytic structures that mimic the binding pockets of natural enzymes or which simply present catalytic motifs at high density on nanostructure scaffolds. Research on these topics is summarized, along with a discussion of metal nanoparticle catalysts templated by peptide nanostructures, especially fibrils. Research showing the high activities of different classes of peptides in catalyzing many reactions is highlighted. Advances in peptide design and synthesis methods mean they hold great potential for future developments of effective bioinspired and biocompatible catalysts.

| S-EPMC8154259 | biostudies-literature

Promoter architecture dictates cell-to-cell variability in gene expression.

Project description:Variability in gene expression among genetically identical cells has emerged as a central preoccupation in the study of gene regulation; however, a divide exists between the predictions of molecular models of prokaryotic transcriptional regulation and genome-wide experimental studies suggesting that this variability is indifferent to the underlying regulatory architecture. We constructed a set of promoters in Escherichia coli in which promoter strength, transcription factor binding strength, and transcription factor copy numbers are systematically varied, and used messenger RNA (mRNA) fluorescence in situ hybridization to observe how these changes affected variability in gene expression. Our parameter-free models predicted the observed variability; hence, the molecular details of transcription dictate variability in mRNA expression, and transcriptional noise is specifically tunable and thus represents an evolutionarily accessible phenotypic parameter.

| S-EPMC4388425 | biostudies-literature

Snake venom-defined fibrin architecture dictates fibroblast survival and differentiation.

Project description:Fibrin is the provisional matrix formed after injury, setting the trajectory for the subsequent stages of wound healing. It is commonly used as a wound sealant and a natural hydrogel for three-dimensional (3D) biophysical studies. However, the traditional thrombin-driven fibrin systems are poorly controlled. Therefore, the precise roles of fibrin's biophysical properties on fibroblast functions, which underlie healing outcomes, are unknown. Here, we establish a snake venom-controlled fibrin system with precisely and independently tuned architectural and mechanical properties. Employing this defined system, we show that fibrin architecture influences fibroblast survival, spreading phenotype, and differentiation. A fine fibrin architecture is a key prerequisite for fibroblast differentiation, while a coarse architecture induces cell loss and disengages fibroblast's sensitivity towards TGF-β1. Our results demonstrate that snake venom-controlled fibrin can precisely control fibroblast differentiation. Applying these biophysical principles to fibrin sealants has translational significance in regenerative medicine and tissue engineering.

| S-EPMC9950370 | biostudies-literature

The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy.

Project description:Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and α-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a β-sheet arrangement reminiscent of the β-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods.

| S-EPMC4388266 | biostudies-literature

Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation.

Project description:A large group of hormones are stored as amyloid fibrils in acidic secretion vesicles before they are released into the bloodstream and readopt their functional state. Here, we identify an evolutionarily conserved hexapeptide sequence as the major aggregation-prone region (APR) of gastrointestinal peptides of the glucagon family: xFxxWL. We determine nine polymorphic crystal structures of the APR segments of glucagon-like peptides 1 and 2, and exendin and its derivatives. We follow amyloid formation by CD, FTIR, ThT assays, and AFM. We propose that the pH-dependent changes of the protonation states of glutamate/aspartate residues of APRs initiate switching between the amyloid and the folded, monomeric forms of the hormones. We find that pH sensitivity diminishes in the absence of acidic gatekeepers and amyloid formation progresses over a broad pH range. Our results highlight the dual role of short aggregation core motifs in reversible amyloid formation and receptor binding.

| S-EPMC10394066 | biostudies-literature

Peptide amyloid surface display.

Project description:Homomeric self-assembly of peptides into amyloid fibers is a feature of many diseases. A central role has been suggested for the lateral fiber surface affecting gains of toxic function. To investigate this, a protein scaffold that presents a discrete, parallel ?-sheet surface for amyloid subdomains up to eight residues in length has been designed. Scaffolds that present the fiber surface of islet amyloid polypeptide (IAPP) were prepared. The designs show sequence-specific surface effects apparent in that they gain the capacity to attenuate rates of IAPP self-assembly in solution and affect IAPP-induced toxicity in insulin-secreting cells.

| S-EPMC4318585 | 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