A conservative mutant of a proteolytic fragment produced during fibril formation enhances fibrillogenesis

Егоров, Владимир В.; Лебедев, Д. В.; Shaldzhyan, Aram A.; Сироткин, А. К.; Горшков, А. Н.; Mirgorodskaya, O. A.; Грудинина, Н. А.; Васин, А. В.; Shavlovsky, M. M.

doi:10.4161/19336896.2014.983745

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…Fibrillogenesis of a peptide corresponding to residues 35–51 of human α-LA (1GYDTQAIVENNESTEYG17, WT peptide) at pH 2 can be dramatically enhanced by the addition of a tetrapeptide TDYG (R peptide) homologous to its C-terminus (TEYG) [ 139 ]. Computer simulations showed that WT peptide can form oligomeric β-like structures due to interactions of the tyrosine residues in the mirror symmetric tails (GYDT and TEYG) of the peptide molecules in antiparallel orientation.…”

Section: Fibrillation Of α-Lactalbumin; Nanoparticles and Nanotubementioning

confidence: 99%

“…Computer simulations showed that WT peptide can form oligomeric β-like structures due to interactions of the tyrosine residues in the mirror symmetric tails (GYDT and TEYG) of the peptide molecules in antiparallel orientation. The authors suggested that peptide R could more rapidly interact with the 1GYDT4 part of WT, stabilizing it in conformation predisposed to oligomerization due to more rapid diffusion and lack of steric interference [ 139 ].…”

Section: Fibrillation Of α-Lactalbumin; Nanoparticles and Nanotubementioning

confidence: 99%

“…SDS concentrations above 0.2 mM many times (~60) increased the lag time, but fibril elongation was accelerated by 3 to 6 fold. SDS concentrations higher than 2 mM inhibited α-LA fibrillation and caused the formation of amorphous aggregates [ 139 ]. Electrostatic interaction of the SDS anion with positive surface groups of the protein can completely unfold its secondary and tertiary structures, which is followed by protein chain restructuration to α-helices [ 141 ].…”

Section: Fibrillation Of α-Lactalbumin; Nanoparticles and Nanotubementioning

confidence: 99%

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α-Lactalbumin, Amazing Calcium-Binding Protein

Permyakov

2020

Biomolecules

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α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4–5), Ca2+-binding protein. α-LA is a regulatory component of lactose synthase enzyme system functioning in the lactating mammary gland. The protein possesses a single strong Ca2+-binding site, which can also bind Mg2+, Mn2+, Na+, K+, and some other metal cations. It contains several distinct Zn2+-binding sites. Physical properties of α-LA strongly depend on the occupation of its metal binding sites by metal ions. In the absence of bound metal ions, α-LA is in the molten globule-like state. The binding of metal ions, and especially of Ca2+, increases stability of α-LA against the action of heat, various denaturing agents and proteases, while the binding of Zn2+ to the Ca2+-loaded protein decreases its stability and causes its aggregation. At pH 2, the protein is in the classical molten globule state. α-LA can associate with membranes at neutral or slightly acidic pH at physiological temperatures. Depending on external conditions, α-LA can form amyloid fibrils, amorphous aggregates, nanoparticles, and nanotubes. Some of these aggregated states of α-LA can be used in practical applications such as drug delivery to tissues and organs. α-LA and some of its fragments possess bactericidal and antiviral activities. Complexes of partially unfolded α-LA with oleic acid are cytotoxic to various tumor and bacterial cells. α-LA in the cytotoxic complexes plays a role of a delivery carrier of cytotoxic fatty acid molecules into tumor and bacterial cells across the cell membrane. Perhaps in the future the complexes of α-LA with oleic acid will be used for development of new anti-cancer drugs.

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Section: Fibrillation Of α-Lactalbumin; Nanoparticles and Nanotubementioning

confidence: 99%

Section: Fibrillation Of α-Lactalbumin; Nanoparticles and Nanotubementioning

confidence: 99%

Section: Fibrillation Of α-Lactalbumin; Nanoparticles and Nanotubementioning

confidence: 99%

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α-Lactalbumin, Amazing Calcium-Binding Protein

Permyakov

2020

Biomolecules

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“…The induction of conformational transitions can also be caused by amyloidogenic protein fragments (Figures 4 and 5 ). This has been specifically shown for the Syrian hamster prion protein PrP [ 27 ] and alpha-lactalbumin [ 28 , 29 ]; it has also been shown that the NAGDVAFV peptide fibrils of lactoferrin are capable of inducing specific binding to the whole protein [ 30 ], while lysozyme fibrillogenesis is accelerated by the nicking or adding of fragments formed after its autohydrolysis by aspartate [ 31 ].…”

Section: Induction Of Conformational Transitionsmentioning

confidence: 99%

“…It is interesting to note that those peptides for the prion protein PrP [ 27 ], alpha-lactalbumin [ 28 , 29 ], and PB1 [ 32 ], all of which are capable of inducing a parent protein conformational transition, contain mirror-symmetrical motifs (MSMs) within their primary structures ( Figure 6 ) [ 34 ]. Mirror-symmetrical motif formation can arise due to amplification of repeats in DNA and have a role in the formation of the tertiary structure in proteins [ 35 ].…”

Section: Induction Of Conformational Transitionsmentioning

confidence: 99%

Peptide-Induced Amyloid-Like Conformational Transitions in Proteins

Егоров

Грудинина

Васин

et al. 2015

International Journal of Peptides

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Changes in protein conformation can occur both as part of normal protein functioning and during disease pathogenesis. The most common conformational diseases are amyloidoses. Sometimes the development of a number of diseases which are not traditionally related to amyloidoses is associated with amyloid-like conformational transitions of proteins. Also, amyloid-like aggregates take part in normal physiological processes such as memorization and cell signaling. Several primary structural features of a protein are involved in conformational transitions. Also the protein proteolytic fragments can cause the conformational transitions in the protein. Short peptides which could be produced during the protein life cycle or which are encoded by short open reading frames can affect the protein conformation and function.

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Nicking and fragmentation are responsible for α‐lactalbumin amyloid fibril formation at acidic pH and elevated temperature

Rahamtullah

Mishra

2021

Protein Science

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Amyloid fibrils are ordered aggregates that may be formed from disordered, partially unfolded, and fragments of proteins and peptides. There are several diseases, which are due to the formation and deposition of insoluble β‐sheet protein aggregates in various tissue, collectively known as amyloidosis. Here, we have used bovine α‐lactalbumin as a model protein to understand the mechanism of amyloid fibril formation at pH 1.6 and 65°C under non‐reducing conditions. Amyloid fibril formation is confirmed by Thioflavin T fluorescence and atomic force microscopy (AFM). Our finding demonstrates that hydrolysis of peptide bonds occurs under these conditions, which results in nicking and fragmentation. The nicking and fragmentation have been confirmed on non‐reducing and reducing gel. We have identified the fragments by matrix‐assisted laser desorption ionization‐time of flight (MALDI‐TOF) mass spectrometry. The fragmentation may initiate nucleation as it coincides with AFM images. Conformational changes associated with monomer resulting in fibrillation are shown by circular dichroism and Raman spectroscopy. The current study highlights the importance of nicking and fragmentation in amyloid fibril formation, which may help understand the role of acidic pH and proteolysis under in vivo conditions in the initiation of amyloid fibril formation.

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A conservative mutant of a proteolytic fragment produced during fibril formation enhances fibrillogenesis

Cited by 6 publications

References 19 publications

α-Lactalbumin, Amazing Calcium-Binding Protein

α-Lactalbumin, Amazing Calcium-Binding Protein

Peptide-Induced Amyloid-Like Conformational Transitions in Proteins

Nicking and fragmentation are responsible for α‐lactalbumin amyloid fibril formation at acidic pH and elevated temperature

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