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An unknown aspect of protein misfolding and topological organization and symmetry of an amyloid fibril itself which could be helpful to study the polymorphism of protein non-native [beta]-pleated aggregates are described.

ATP acts as a biological hydrotrope preventing protein aggregation. Here, we report a novel chimeric peptide, ACC1–13K8, with an unusual capacity to bind and incorporate ATP while self-assembling into amyloid fibrils. The amino acid sequence combines a highly amyloidogenic segment of insulin's A-chain (ACC1–13) and octalysine (K8). Fibrillization requires binding 2 ATP molecules per ACC1–13K8 monomer and is not triggered by adenosine di- and monophosphates (ADP, AMP). Infrared and CD spectra and AFM-based morphological analysis reveal tight and orderly entrapment of ATP within superstructural hybrid peptide–ATP fibrils. The incorporation of ATP is an emergent property of ACC1–13K8 not observed for ACC1–13 and K8 segments separately. We demonstrate how new functionalities (e.g. ATP storage) emerge from synergistic coupling of amyloidogenic segments with non-amyloidogenic peptide ligands, and suggest that ATP's role in protein misfolding is more nuanced than previously assumed. [ABSTRACT FROM AUTHOR]

A detailed thermodynamic study of an aggregation-prone polypeptide, polylysine, is performed to gain a deeper insight into the scenario of physicochemical events during its unfolding, aggregation, and amyloidogenesis. The precise and simultaneous determination of the partial molar volume, the heat capacity and the coefficients of thermal expansion as well as adiabatic and isothermal compressibility of the protein upon unfolding and aggregation yields a thermodynamic aggregation process highlighting the importance of volume fluctuations during unfolding and amyloidogenesis of proteins.

Atomic force microscopy images and dynamic light scattering measurements are used to understand the mechanism underlying the solubilization of insulin fibrils by the aqueous solutions of dimethyl sulfoxide (DMSO) without perturbing their [beta]-pleated structure. The findings revealed that the DMSO-induced ensembles of insulin molecules are closely related to elementary building blocks of amyloid fibrils.

The denaturated state of an [alpha]-helical protein, insulin, has converted to a non-native [beta]-sheet-rich structure upon de novo 'refolding' in an anhydrous environment. The results have shown that folding in the absence of water has resulted in inefficient burial of hydrophobic side-chains and thermodynamic frustration at the water-protein interface.

The resonance Raman spectra for various complexes are studied to analyze the formation of an intensely violet inclusion complex of insulin amyloid fibrils and molecular iodine, which acts as a misfolded protein and a nanoscale scaffold. The analysis provides a new tool for studying the amyloids and also presents a new model for designing the protein-based drug delivery media by explaining the molecular basis of their varying strain-dependent biological activity.

A model cosolvent, ethanol, has profound and diversified effects on the amyloidogenic self-assembly of insulin, yielding spectroscopically and morphologically distinguishable forms of beta-aggregates. The alcohol reduces hydrodynamic radii of insulin molecules, decreases enthalpic costs associated with aggregation-prone intermediate states, and accelerates the aggregation itself.

The D20(FTIR) spectra of polylysine in beta-sheet conformation are virtually identical, which implies that antiparallel fold is maintained upon the diastereomeric self-assembly. The high-pressure FTIR spectroscopy showed a marked stabilization of the polylysine's beta-sheet structure against pressure.