Determination of amyloid core regions of insulin analogues fibrils

Surin, Alexey K.; Grishin, Sergei Y.; Galzitskaya, Oxana V.

doi:10.1080/19336896.2020.1776062

Cited by 14 publications

(13 citation statements)

References 87 publications

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“…Thus, it is known that amyloidogenic peptides, like antimicrobial peptides, can have a toxic effect on bacterial cells [52]. In addition, the amino acid sequences included in the spine of amyloid fibrils are sufficiently resistant to the action of proteases, which is one of the diagnostic properties of amyloid fibrils [53,54]. This resistance can also be useful for antimicrobial peptides, allowing them to be protected from the action of exopeptidases [55].…”

Section: Introductionmentioning

confidence: 99%

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Grishin

Domnin

Кравченко

et al. 2021

IJMS

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The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as Pseudomonas aeruginosa, Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against P. aeruginosa.

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Section: Introductionmentioning

confidence: 99%

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Grishin

Domnin

Кравченко

et al. 2021

IJMS

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“…It is interesting to note that the very powerful tendency to aggregate both A–B and B–A peptides eludes the TANGO and Waltz algorithms ( Figure 1 B). On the other hand, in their extensive screening study of various amyloidogenic regions in insulin, Surin et al 57 noted an increased amyloidogenic potential within the A2–A12 region according to the data obtained by application of PASTA 2.0 58 and ZipperDB algorithms. 29 , 59 …”

Section: Resultsmentioning

confidence: 99%

Extremely Amyloidogenic Single-Chain Analogues of Insulin’s H-Fragment: Structural Adaptability of an Amyloid Stretch

Dec

Dzwolak

2020

Langmuir

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Relatively short amino acid sequences often play a pivotal role in triggering protein aggregation leading to the formation of amyloid fibrils. In the case of insulin, various regions of A- and B-chains have been implicated as the most relevant to the protein’s amyloidogenicity. Here, we focus on the highly amyloidogenic H-fragment of insulin comprising the disulfide-bonded N-terminal parts of both chains. Analysis of the aggregation behavior of single-chain peptide derivatives of the H-fragment suggests that the A-chain’s part initiates the aggregation process while the disulfide-tethered B-chain reluctantly adapts to amyloid structure. Merging of both A- and B-parts into single-chain continuous peptides (A–B and B–A) results in extreme amyloidogenicity exceeding that of the double-chain H-fragment as reflected by almost instantaneous de novo fibrillization. Amyloid fibrils of A–B and B–A present distinct morphological and infrared traits and do not cross-seed insulin. Our study suggests that the N-terminal part of insulin’s A-chain containing the intact Cys6–Cys11 intrachain disulfide bond may constitute insulin’s major amyloid stretch which, through its bent conformation, enforces a parallel in-register alignment of β-strands. Comparison of the self-association behavior of H, A–B, and B–A peptides suggests that A-chain’s N-terminal amyloid stretch is very versatile and adaptive to various structural contexts.

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“…The results of the digestion experiments can be monitored with several techniques, such as SDS-PAGE and protein immunoblotting, mass spectrometry, or electron microscopy. In some cases, a mixture of proteases can be used instead of proteinase K to identify the core of amyloid fibrils (Selivanova et al, 2016;Surin et al, 2020).…”

Section: Proteinase K and Mixture Of Proteases Digestionmentioning

confidence: 99%

MIRRAGGE – Minimum Information Required for Reproducible AGGregation Experiments

Martins

Navarro

Silva

et al. 2020

Front. Mol. Neurosci.

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Reports on phase separation and amyloid formation for multiple proteins and aggregation-prone peptides are recurrently used to explore the molecular mechanisms associated with several human diseases. The information conveyed by these reports can be used directly in translational investigation, e.g., for the design of better drug screening strategies, or be compiled in databases for benchmarking novel aggregation-predicting algorithms. Given that minute protocol variations determine different outcomes of protein aggregation assays, there is a strong urge for standardized descriptions of the different types of aggregates and the detailed methods used in their production. In an attempt to address this need, we assembled the Minimum Information Required for Reproducible Aggregation Experiments (MIRRAGGE) guidelines, considering first-principles and the established literature on protein self-assembly and aggregation. This consensus information aims to cover the major and subtle determinants of experimental reproducibility while avoiding excessive technical details that are of limited practical interest for non-specialized users. The MIRRAGGE table (template available in Supplementary Information) is useful as a guide for the design of new studies and as a checklist during submission of experimental reports for publication. Full disclosure of relevant information also enables other researchers to reproduce results correctly and facilitates systematic data deposition into curated databases.

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Determination of amyloid core regions of insulin analogues fibrils

Cited by 14 publications

References 87 publications

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Extremely Amyloidogenic Single-Chain Analogues of Insulin’s H-Fragment: Structural Adaptability of an Amyloid Stretch

MIRRAGGE – Minimum Information Required for Reproducible AGGregation Experiments

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