Acceleration of protein aggregation by amphiphilic peptides: Transformation of supramolecular structure of the aggregates

Abstract

Protein self-assembly and aggregation represent a special tool in biomedicine and biotechnology to produce biological materials for a wide range of applications. The protein aggregates are very different morphologically, varying from soluble amorphous aggregates to highly ordered amyloid-like fibrils, the latter being associated with molecular structures able to perform specific functions in living systems. Fabrication of novel biomaterials resembling natural protein assemblies has awakened interest in identification of low-molecular-weight biogenic agents as regulators of transformation of aggregation-prone proteins into fibrillar structures. Short amphiphilic peptides can be considered for this role. Using dynamic light scattering, turbidimetry, fluorescence spectroscopy, and transmission electron microscopy (TEM), we have demonstrated that the Arg-Phe dipeptide dramatically accelerates the aggregation of a model protein, α-lactalbumin, to generate morphologically different structures. TEM revealed transformation of spherical particles observed in the control samples into branched chains of fibril-like nanostructures in the presence of the peptide, suggesting that amphiphilic peptides can induce changes in the physicochemical properties of a protein substrate (net charge, hydrophobicity, and tendency to β-structure formation) resulting in accumulation of peptide-protein complexes competent to self-assembly into supramolecular structures. A number of other short amphiphilic peptides have also been shown to accelerate the aggregation process, using alternative complementary protein substrates for identification of molecular recognition modules. Peptide-protein assemblies are suggested to play the role of building blocks for formation of supramolecular structures profoundly differing from those of the individual protein substrate in type, size, and shape.

Formation of supramolecular structures of a native‐like protein in the presence of amphiphilic peptides: Variations in aggregate morphology

“…We have previously detected formation of similar “baroque pearl chains” structures in the processes of aggregation of a small acidic globular protein, α‐lactalbumin, induced by the positively charged Arg‐Phe dipeptide, and of a highly basic globular protein, hen egg white lysozyme, in the presence of the negatively charged Asp‐Phe dipeptide [22]. In the present study, we have used TEM to make a more close study of morphological features of the aggregates of α‐lactalbumin or lysozyme, respectively (Supplementary Fig.…”

“…We have recently demonstrated that the interaction of amphiphilic peptides with oppositely charged aggregation‐prone proteins resulted in acceleration of the aggregation process [22]. In the present work, our aim was to study whether short amphiphilic peptides possess the potential to induce aggregation in vitro of native‐like proteins under physiologically relevant conditions.…”

The αA66–80 Peptide Interacts with Soluble α-Crystallin and Induces Its Aggregation and Precipitation: A Contribution to Age-Related Cataract Formation

“…Such aggregation and insolubilization of soluble proteins by peptides with amyloidogenic potential has been reported earlier. 23,24,46 …”

α-Lactalbumin, Amazing Calcium-Binding Protein

“…Crocin and safranal, small organic molecules from Crocus sativus , inhibit formation of soluble oligomers and fibrillar assemblies of α-LA [ 144 ]. Arg-Phe dipeptide dramatically accelerates the aggregation of α-LA and generates various structures [ 145 ]. It was revealed that a transformation of spherical particles observed in the control samples into branched chains of fibril-like nanostructures in the presence of the peptide.…”