Identification of Regions in Apomyoglobin that Form Intermolecular Interactions in Amyloid Aggregates Using High-Performance Mass Spectrometry

Katina, N. S.; Suvorina, Mariya Yu.; Grigorashvili, Elizaveta I.; Marchenkov, Victor V.; Ryabova, N. A.; Nikulin, Alexei; Surin, Alexey K.

doi:10.1134/s1061934817130056

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…The above result was consistent with the finding in a prior study that the change in the standard free energy of denaturation brought by the addition of glycerol increases in aqueous solutions (9). Recently, Katina et al demonstrated that A-, B-, E-, F-, and G-helices in the native apomyoglobin structure participate in intermolecular interactions in amyloids (47). Therefore, the suppression of amyloid-like oligomerization by glycerol observed at a relatively low concentration might suggest a specific interaction between glycerol and local domains of the protein to prohibit direct interaction between the proteins.…”

Section: Discussionsupporting

confidence: 92%

Direct Evidence for the Effect of Glycerol on Protein Hydration and Thermal Structural Transition

Hirai

Ajito

Sugiyama

et al. 2018

Biophysical Journal

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The mechanisms of protein stabilization by uncharged solutes, such as polyols and sugars, have been intensively studied with respect to the chemical thermodynamics of molecular crowding. In particular, many experimental and theoretical studies have been conducted to explain the mechanism of the protective action on protein structures by glycerol through the relationship between hydration and glycerol solvation on protein surfaces. We used wide-angle x-ray scattering (WAXS), small-angle neutron scattering, and theoretical scattering function simulation to quantitatively characterize the hydration and/or solvation shell of myoglobin in aqueous solutions of up to 75% v/v glycerol. At glycerol concentrations below ∼40% v/v, the preservation of the hydration shell was dominant, which was reasonably explained by the preferential exclusion of glycerol from the protein surface (preferential hydration). In contrast, at concentrations above 50% v/v, the partial penetration or replacement of glycerol into or with hydration-shell water (neutral solvation by glycerol) was gradually promoted. WAXS results quantitatively demonstrated the neutral solvation, in which the replacement of hydrated water by glycerol was proportional to the volume fraction of glycerol in the solvent multiplied by an exchange rate (β ≤ 1). These phenomena were confirmed by small-angle neutron scattering measurements. The observed WAXS data covered the entire hierarchical structure of myoglobin, ranging from tertiary to secondary structures. We separately analyzed the effect of glycerol on the thermal stability of myoglobin at each hierarchical structural level. The thermal transition midpoint temperature at each hierarchical structural level was raised depending on the glycerol concentration, with enhanced transition cooperativeness between different hierarchical structural levels. The onset temperature of the helix-to-cross β-sheet transition (the initial process of amyloid formation) was evidently elevated. However, oligomerization connected to fibril formation was suppressed, even at a low glycerol concentration.

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Section: Discussionsupporting

confidence: 92%

Direct Evidence for the Effect of Glycerol on Protein Hydration and Thermal Structural Transition

Hirai

Ajito

Sugiyama

et al. 2018

Biophysical Journal

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“…In general, we can say that despite the small differences in the spine of fibrils that we offer for insulin and its analogues, using mass spectrometry it was not possible to identify sequences that can be interpreted as amyloidogenic in the local sites of the amino acid modifications of lispro and glargine. Some polymorphism in the sequences can be explained by the nonspecificity of the action of proteases, which was already noted in other works [65,66].…”

Section: Discussionsupporting

confidence: 61%

Determination of amyloid core regions of insulin analogues fibrils

Surin

Grishin

Galzitskaya

2020

Prion

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A rapid-acting insulin lispro and long-acting insulin glargine are commonly used for the treatment of diabetes. Clinical cases have described the formation of injectable amyloidosis with these insulin analogues, but their amyloid core regions of fibrils were unknown. To reveal these regions, we have analysed the hydrolyzates of insulin fibrils and its analogues using high-performance liquid chromatography and mass spectrometry methods and found that insulin and its analogues have almost identical amyloid core regions that intersect with the predicted amyloidogenic regions. The obtained results can be used to create new insulin analogues with a low ability to form fibrils. Abbreviations: a.a., amino acid residues; HPLC-MS, high-performance liquid chromatography/ mass spectrometry; m/z, mass-to-charge ratio; TEM, transmission electron microscopy.

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“…From our point of view, the AIITGIVVDI, SWIVLEAAFA, ITDFGIFIGL, LHITDMAWKR peptides were of interest for the synthesis and experimental verification of amyloidogenic properties. One should take into account both the differences in the algorithms for predicting amyloidogenic regions by the FoldAmyloid [ 38 ], Waltz [ 39 ], Pasta 2.0 [ 40 ], and AGGRESCAN [ 41 ] programs, and the possible effects of nonspecific hydrolysis of protein sequence regions by proteases, in particular, Proteinase K [ 54 , 55 ]. In this regard, the synthesized peptides AIITGIVVDI, SWIVLEAAFA, ITDFGIFIGL, LHITDMAWKR were also tested by other methods for detecting amyloids, namely EM and fluorescence spectroscopy with ThT.…”

Section: Discussionmentioning

confidence: 99%

Identification of Amyloidogenic Regions in Pseudomonas aeruginosa Ribosomal S1 Protein

Grishin

Dzhus

Glukhov

et al. 2021

IJMS

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Bacterial S1 protein is a functionally important ribosomal protein. It is a part of the 30S ribosomal subunit and is also able to interact with mRNA and tmRNA. An important feature of the S1 protein family is a strong tendency towards aggregation. To study the amyloidogenic properties of S1, we isolated and purified the recombinant ribosomal S1 protein of Pseudomonas aeruginosa. Using the FoldAmyloid, Waltz, Pasta 2.0, and AGGRESCAN programs, amyloidogenic regions of the protein were predicted, which play a key role in its aggregation. The method of limited proteolysis in combination with high performance liquid chromatography and mass spectrometric analysis of the products, made it possible to identify regions of the S1 protein from P. aeruginosa that are protected from the action of proteinase K, trypsin, and chymotrypsin. Sequences of theoretically predicted and experimentally identified amyloidogenic regions were used to synthesize four peptides, three of which demonstrated the ability to form amyloid-like fibrils, as shown by electron microscopy and fluorescence spectroscopy. The identified amyloidogenic sites can further serve as a basis for the development of new antibacterial peptides against the pathogenic microorganism P. aeruginosa.

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Identification of Regions in Apomyoglobin that Form Intermolecular Interactions in Amyloid Aggregates Using High-Performance Mass Spectrometry

Cited by 6 publications

References 30 publications

Direct Evidence for the Effect of Glycerol on Protein Hydration and Thermal Structural Transition

Direct Evidence for the Effect of Glycerol on Protein Hydration and Thermal Structural Transition

Determination of amyloid core regions of insulin analogues fibrils

Identification of Amyloidogenic Regions in Pseudomonas aeruginosa Ribosomal S1 Protein

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