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

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.

Paradoxical acceleration of dithiothreitol-induced aggregation of insulin in the presence of a chaperone.

The kinetics of dithiothreitol (DTT)-induced aggregation of human recombinant insulin and the effect of α-crystallin, a representative of the family of small heat shock proteins, on the aggregation process have been studied using dynamic light scattering technique. Analysis of the distribution of the particles by size measured in the course of aggregation showed that the initial stage of the aggregation process was the stage of formation of the start aggregates with a hydrodynamic radius (R(h)) of about 90 nm. When studying the effect of α-crystallin on the rate of DTT-induced aggregation of insulin, it was demonstrated that low concentrations of α-crystallin dramatically accelerated the aggregation process, whereas high concentrations of α-crystallin suppressed insulin aggregation.

Mechanism of suppression of dithiothreitol-induced aggregation of bovine alpha-lactalbumin by alpha-crystallin.

The kinetics of dithiothreitol (DTT)-induced aggregation of alpha-lactalbumin from bovine milk has been studied using dynamic light-scattering technique. Analysis of the distribution of the particles formed in the solution of alpha-lactalbumin after the addition of DTT by size showed that the initial stage of the aggregation process was the stage of formation of the start aggregates with the hydrodynamic radius (R(h)) of 80-100nm. Further growth of the protein aggregates proceeds as a result of sticking of the start aggregates.

Opioid peptides derived from food proteins suppress aggregation and promote reactivation of partly unfolded stressed proteins.

A new view of the opioid peptides is presented. The potential of small peptides derived from precursor food proteins, to bind to partly unfolded stressed proteins to prevent their irreversible aggregation and inactivation has been demonstrated in various in vitro test systems: dithiothreitol-induced aggregation of alpha-lactalbumin (LA), heat-induced aggregation of alcohol dehydrogenase (ADH), and aggregation and inactivation of bovine erythrocyte carbonic anhydrase (CA) in the process of its refolding after removal of stress conditions. Using dynamic light scattering (DLS), turbidimetry, fluorescence, and circular dichroism measurements protective effects of the synthetic opioid peptides: exorphin C from wheat gluten (Tyr-Pro-Ile-Ser-Leu), rubiscolin-5 from spinach ribulose-bisphosphate-carboxylase/oxygenase (Rubisco) (Tyr-Pro-Leu-Asp-Leu), and hemorphin-6 from bovine hemoglobin (Tyr-Pro-Trp-Thr-Gln-Arg) have been revealed.

Protein aggregates as depots for the release of biologically active compounds.

Protein misfolding and aggregation is one of the most serious problems in cell biology, molecular medicine, and biotechnology. Misfolded proteins interact with each other or with other proteins in non-productive or damaging ways. However, a new paradigm arises that protein aggregation may be exploited by nature to perform specific functions in different biological contexts.