RESUMEN
Carbon nanotubes have specific properties that make them potentially useful in biomedicine and biotechnology. However, carbon nanotubes may themselves be toxic, making it imperative to understand how carbon nanotubes interact with biomolecules such as proteins. Here, we used NMR, CD, and ThT/fluorescence spectroscopy together with AFM imaging to study pH-dependent molecular interactions between single walled carbon nanotubes (SWNTs) and the amyloid-beta (Aß) peptide. The aggregation of the Aß peptide, first into oligomers and later into amyloid fibrils, is considered to be the toxic mechanism behind Alzheimer's disease. We found that SWNTs direct the Aß peptides to form a new class of ß-sheet-rich yet non-amyloid fibrils.
Asunto(s)
Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/ultraestructura , Amiloide/química , Amiloide/ultraestructura , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestructura , Fragmentos de Péptidos/química , Fragmentos de Péptidos/ultraestructura , Sitios de Unión , Ensayo de Materiales , Complejos Multiproteicos/química , Complejos Multiproteicos/ultraestructura , Unión Proteica , Conformación ProteicaRESUMEN
The icosahedrally symmetrized structure of bacteriophage MS2 as determined by cryo-electron microscopy (EM) reveals the presence of genomic RNA that attaches to coat-protein dimers. Earlier X-ray diffraction studies revealed similar interactions between the unique operator hairpin of the MS2 genomic RNA and the coat-protein dimer. This observation leads us to conclude that not only the operator, but also many other RNA sequences in the genome of MS2, are able to bind to the coat-protein dimer. A substantial number of potential coat-protein-dimer binding sites are present in the genome of MS2 that can account for the observed RNA densities in the EM map. Moreover, it appears that these stem-loop structures are able to bind in a similar fashion to the coat protein dimer as the wild-type operator hairpin. The EM map also shows additional density between the potential operator-binding sites, linking the RNA stem-loops together to form an icosahedral network around the 3 and 5-fold axes. This RNA network is bound to the inside of the MS2 capsid and probably influences both capsid stability and formation, supporting the idea that capsid formation and RNA packaging are intimately linked to each other.
