The presence of cross-β-structure as a key determinant of carbonic anhydrase amyloid fibrils cytotoxicity

Fakhranurova, Liliia I.; Balobanov, Vitaly A.; Ryabova, N. A.; Glukhov, Anatoly S.; Ilyina, Nelly B.; Markelova, Natalia; Marchenkov, Victor V.; Katina, N. S.

doi:10.1016/j.bbrc.2020.01.113

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…The amino acid sequence is believed to play a key role in achieving the correct structure and function of antimicrobial peptides [56]. However, amyloidogenic peptides can have a toxic effects on eukaryotic cells [57,58], which is an undesirable effect for the future use of AMPs in medicine [59]. Thus, the creation of a new generation of amyloidogenic-antimicrobial peptides requires studying how amyloidogenic and antimicrobial amino acid sequences can interact as part of a single molecule.…”

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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“…The plasmid pET-11c_joe encoding BCAB was expressed in E. coli BL21DE3 cells at 37 °C. According to the early method, the protein was purified by anion exchange chromatography and gel-filtration [ 32 ]. In this work, the apo-form of BCAB was used.…”

Section: Methodsmentioning

confidence: 99%

“…Our work aimed to investigate the aggregation of a large model protein, bovine carbonic anhydrase B (BCAB), which serves as a convenient model with a well-described folding [ 29 , 30 , 31 ]. Because BCAB is one of a few proteins forming cytotoxic fibrils, identifying the specificities of this protein aggregation could help us to understand the mechanism of cell damage in amyloidosis [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Under Conditions of Amyloid Formation Bovine Carbonic Anhydrase B Undergoes Fragmentation by Acid Hydrolysis

et al. 2021

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The development of many severe human diseases is associated with the formation of amyloid fibrils. Most of the available information on the process of amyloid formation has been obtained from studies of small proteins and peptides, wherein the features of complex proteins’ aggregation remain insufficiently investigated. Our work aimed to research the amyloid aggregation of a large model protein, bovine carbonic anhydrase B (BCAB). It has previously been demonstrated that, when exposed to an acidic pH and elevated temperature, this protein forms amyloid fibrils. Here, we show that, under these conditions and before amyloid formation, BCAB undergoes fragmentation by acid hydrolysis to give free individual peptides and associated peptides. Fragments in associates contain a pronounced secondary structure and act as the main precursor of amyloid fibrils, wherein free peptides adopt mostly unstructured conformation and form predominantly irregular globular aggregates. Reduced acidity decreases the extent of acid hydrolysis, causing BCAB to form amorphous aggregates lacking the thioflavin T binding β-structure. The presented results provide new information on BCAB amyloid formation and show the importance of protein integrity control when working even in mildly acidic conditions.

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Carbonic anhydrase amyloid fibrils composed of laterally associated protofilaments show reduced cytotoxicity

Ryabova

Fakhranurova

Balobanov

et al. 2022

Biochemical and Biophysical Research Communications

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The presence of cross-β-structure as a key determinant of carbonic anhydrase amyloid fibrils cytotoxicity

Cited by 4 publications

References 28 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?

Under Conditions of Amyloid Formation Bovine Carbonic Anhydrase B Undergoes Fragmentation by Acid Hydrolysis

Carbonic anhydrase amyloid fibrils composed of laterally associated protofilaments show reduced cytotoxicity

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