Structural Characterisation of Amyloidogenic Intrinsically Disordered Zinc Finger Protein Isoforms DPF3b and DPF3a
Double PHD Finger 3 (DPF3), Intrinsically Disordered Protein, Spectroscopy, Protein Aggregation, Amyloid Fibril
Digital Object Identifier (DOI)
Double PHD fingers 3 (DPF3) is a zinc finger protein, found in the BAF chromatin remodelling complex, and is involved in the regulation of gene expression. Two DPF3 isoforms have been identified, respectively named DPF3b and DPF3a. Very limited structural information is available for these isoforms, and their specific functionality still remains poorly studied. In a previous work, we have demonstrated the first evidence of DPF3a being a disordered protein sensitive to amyloid fibrillation. Intrinsically disordered proteins (IDPs) lack a defined tertiary structure, existing as a dynamic conformational ensemble, allowing them to act as hubs in protein-protein interaction networks. In the present study, we have more thoroughly characterised DPF3a in vitro behaviour, as well as unravelled and compared the structural properties of the DPF3b isoform, using an array of predictors and biophysical techniques. Predictions, spectroscopy, and dynamic light scattering have revealed a high content in disorder: prevalence of random coil, aromatic residues partially to fully exposed to the solvent, and large hydrodynamic diameters. DPF3a appears to be more disordered than DPF3b, and exhibits more expanded conformations. Furthermore, we have shown that they both time-dependently aggregate into amyloid fibrils, as revealed by typical circular dichroism, deep-blue autofluorescence, and amyloid-dye binding assay fingerprints. Although spectroscopic and microscopic analyses have unveiled that they share a similar aggregation pathway, DPF3a fibrillates at a faster rate, likely through reordering of its C-terminal domain.
Was this content written or created while at USF?
Citation / Publisher Attribution
International Journal of Biological Macromolecules, v. 218, p. 57-71
Scholar Commons Citation
Mignon, Julien; Mottet, Denis; Leyder, Tanguy; Uversky, Vladimir N.; Perpète, Eric A.; and Michaux, Catherine, "Structural Characterisation of Amyloidogenic Intrinsically Disordered Zinc Finger Protein Isoforms DPF3b and DPF3a" (2022). Molecular Medicine Faculty Publications. 954.