Title
Conformational Conversion during Controlled Oligomerization into Nonamylogenic Protein Nanoparticles
Author
Julieta M. Sánchez, Laura Sánchez-García, Mireia Pesarrodona, Naroa Serna, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Esther Vázquez, Antonio Villaverde
Year
2018
Journal
Biomacromolecules
Abstract
Protein materials are rapidly gaining interest in materials sciences and nanomedicine because of their intrinsic biocompatibility and full biodegradability. The controlled construction of supramolecular entities relies on the controlled oligomerization of individual polypeptides, achievable through different strategies. Because of the potential toxicity of amyloids, those based on alternative molecular organizations are particularly appealing, but the structural bases on nonamylogenic oligomerization remain poorly studied. We have applied spectrofluorimetry and spectropolarimetry to identify the conformational conversion during the oligomerization of His-tagged cationic stretches into regular nanoparticles ranging around 11 nm, useful for tumor-targeted drug delivery. We demonstrate that the novel conformation acquired by the proteins, as building blocks of these supramolecular assemblies, shows different extents of compactness and results in a beta structure enrichment that enhances their structural stability. The conformational profiling presented here offers clear clues for understanding and tailoring the process of nanoparticle formation through the use of cationic and histidine rich stretches in the context of protein materials usable in advanced nanomedical strategies.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Thermal stability, Protein folding, Thermodynamics, Biochemistry