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

Argudo, Pablo G.; Giner‐Casares, Juan J.

doi:10.1039/d0na00941e

Cited by 19 publications

(14 citation statements)

References 179 publications

(228 reference statements)

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“…68 Others suggested that it was unclear whether the β-sheets in amyloid structures are antiparallel or parallel. 10,69 Also, it was discussed whether the low-frequency component around 1697 cm −1 , usually assigned to antiparallel β-sheets, was due to residues of nonfibrillar material. 56 In spider silk systems, the antiparallel character of the β-sheets was confirmed previously.…”

Section: = = °90mentioning

confidence: 99%

“…3 Further, due to their biodegradability, their high tunability, and their ability to form various nanostructures, IDPs are of great interest as synthetic polymer substitutes, 4 scaffolds for tissue regeneration 5 or nanodrugs. 6 On the other hand, intrinsically disordered structures can assemble into well-defined structures, which can be beneficial for an organism, i.e., the gain of function such as in pili of bacteria. 7,8 The assembly can also be disadvantageous, such as in so-called conformational diseases, where it leads to a loss of function like Amyotrophic Lateral Sclerosis, Huntington's disease, or Parkinson's disease to name just a few examples.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The disordering leads to high structural flexibility enabling IDPs and IDRs to be involved in biological functions and processes like the conversion of fibrinogen to fibrin, ribosomal assembly, or allosteric regulation . Further, due to their biodegradability, their high tunability, and their ability to form various nanostructures, IDPs are of great interest as synthetic polymer substitutes, scaffolds for tissue regeneration or nanodrugs …”

Section: Introductionmentioning

confidence: 99%

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β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

et al. 2023

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Intrinsically disordered proteins (IDPs) play an important role in molecular biology and medicine because their induced folding can lead to so-called conformational diseases, where β-amyloids play an important role. Still, the molecular folding process into the different substructures, such as parallel/ antiparallel or extended β-sheet/crossed β-sheet is not fully understood. The recombinant spider silk protein eADF4(Cx) consisting of repeating modules C, which are composed of a crystalline (pep-c) and an amorphous peptide sequence (pep-a), can be used as a model system for IDP since it can assemble into similar structures. In this work, blend films of the pep-c and pep-a sequences were investigated to modulate the β-sheet formation by varying the molar fraction of pep-c and pep-a. Dichroic Fouriertransform infrared spectroscopy (FTIR), circular dichroism, spectroscopic ellipsometry, atomic force microscopy, and IR nanospectroscopy were used to examine the secondary structure, the formation of parallel and antiparallel β-sheets, their orientation, and the microscopic roughness and phase formation within peptide blend films upon methanol post-treatment. New insights into the formation of filament-like structures in these silk blend films were obtained. Filament-like structures could be locally assigned to βsheet-rich structures. Further, the antiparallel or parallel character and the orientation of the formed β-sheets could be clearly determined. Finally, the ideal ratio of pep-a and pep-c sequences found in the fibroin 4 of the major ampullate silk of spiders could also be rationalized by comparing the blend and spider silk protein systems.

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Section: = = °90mentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

et al. 2023

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“…However, α-helical structures, the most common secondary structures of natural proteins, are less exploited for the creation of assembled structures. Short peptides containing unmodified amino acids present weak intrinsic helical stability, which hinders their use to generate self-assembled helical structures [ 51 ]. One of the main strategies involves the use of helix-promoting noncoded amino acids such as β–amino acids and α-aminoisobutyric acid [ 52 ].…”

Section: Self-assembly Processmentioning

confidence: 99%

Self-Assembling Peptides: From Design to Biomedical Applications

Manna

Natale

Onesto

et al. 2021

IJMS

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Self-assembling peptides could be considered a novel class of agents able to harvest an array of micro/nanostructures that are highly attractive in the biomedical field. By modifying their amino acid composition, it is possible to mime several biological functions; when assembled in micro/nanostructures, they can be used for a variety of purposes such as tissue regeneration and engineering or drug delivery to improve drug release and/or stability and to reduce side effects. Other significant advantages of self-assembled peptides involve their biocompatibility and their ability to efficiently target molecular recognition sites. Due to their intrinsic characteristics, self-assembled peptide micro/nanostructures are capable to load both hydrophobic and hydrophilic drugs, and they are suitable to achieve a triggered drug delivery at disease sites by inserting in their structure’s stimuli-responsive moieties. The focus of this review was to summarize the most recent and significant studies on self-assembled peptides with an emphasis on their application in the biomedical field.

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“…Considering these controversial findings about secondary structure supporting peptide fibrillization, a more easily accepted theory has risen that non-β-strand peptides could undergo fibrillization, accompanying which the conformation of peptide monomers also transformed to β-strand. − Following the textbook theory that the secondary structure determines the tertiary structure, it seems to be reasonable to presume that disordered peptide monomers should transform to β-strand conformation before they can self-assemble into nanofibers. However, for these intrinsically disordered peptides, very few research studies have been systematically carried out to clarify the causal link between peptide fibrillization and β-strand conformation, i.e., which one comes first.…”

Section: Introductionmentioning

confidence: 99%

Alternative Causal Link between Peptide Fibrillization and β-Strand Conformation

2021

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In the prevailing phenomenon of peptide fibrillization, β-strand conformation has long been believed to be an important structural basis for peptide assembly. According to a widely accepted theory, in most peptide fibrillization processes, peptide monomers need to intrinsically take or transform to β-strand conformation before they can undergo ordered packing to form nanofibers. In this study, we reported our findings on an alternative peptide fibrillization pathway starting from a disordered secondary structure, which could then transform to β-strand after fibrillization. By using circular dichroism, thioflavin-T binding test, and transmission electron microscopy, we studied the secondary structure and assembly behavior of Ac-RADARADARADARADA-NH 2 (RADA16-I) in a low concentration range. The effects of peptide concentration, solvent polarity, pH, and temperature were investigated in detail. Our results showed that at very low concentrations, even though the peptide was in a disordered secondary structure, it could still form nanofibers through intermolecular assembly, and under higher peptide concentrations, the transformation from the disordered structure to β-strand could happen with the growth of nanofibers. Our results indicated that even without ordered β-strand conformation, driving forces such as hydrophobic interaction and electrostatic interaction could still play a determinative role in the self-assembly of peptides. At least in some cases, the formation of β-strand might be the consequence rather than the cause of peptide fibrillization.

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

Abstract: 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...

Cited by 19 publications

References 179 publications

β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

β-Sheet Structure Formation within Binary Blends of Two Spider Silk Related Peptides

Self-Assembling Peptides: From Design to Biomedical Applications

Alternative Causal Link between Peptide Fibrillization and β-Strand Conformation

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