RESUMEN
Transmissible spongiform encephalopathies (or prion diseases) such as Creutzfeldt-Jacob disease, mad cow disease, and scrapie are characterized by accumulation in the brain of misfolded prion protein aggregates (PrPSc) that have properties of amyloid fibrils. Given that transition metal ions, such as copper and zinc, appear to be important for physiological functions of cellular PrP (PrPC) as well as for prion disease pathogenesis, exploring their role in the protein aggregation process is of considerable interest. Copper(II) in particular is well-known to bind to the four tandem octapeptide repeats (PHGGGWGQ) located in the N-terminal region of PrP (human PrP amino acids 60-91), as well as to additional histidine binding sites outside the octarepeat region with distinct binding modes depending on Cu2+ concentration. Here, using the Y145Stop human prion protein variant (huPrP23-144) as a model and a combination of multidimensional solution and solid-state NMR spectroscopy, atomic force microscopy and thioflavin T fluorescence assays we probed the binding of Cu2+ to monomeric huPrP23-144 and the impact of this binding on fibril assembly kinetics and their structural properties. Remarkably, we found that fibrils formed by huPrP23-144 containing one molar equivalent of bound Cu2+ adopt a core structure that is distinct from that found for huPrP23-144 in the absence of Cu2+ but, instead, corresponds to a conformational strain formed by huPrP23-144 containing the A117V mutation. A similar huPrP23-144 A117V-like amyloid core structure was adopted by a Cu2+-bound Δ51-91 huPrP23-144 deletion variant lacking the entire octarepeat region, suggesting that Cu2+ binding to His residues 96, 111 and 140 located near the C-terminus of huPrP23-144 is primarily responsible for the observed change in fibril conformation, potentially due to partial structuring of the intrinsically disordered huPrP23-144 by the bound Cu2+ during the fibril assembly process. We also found that fibrils formed by Cu2+-bound huPrP23-144 adopt the native huPrP23-144-like rather than A117V-like structure when the fibrillization reaction is seeded with pre-formed huPrP23-144 amyloid.
RESUMEN
Earth-abundant and cheaper zinc-based organometallic molecules as luminophores are drawing significant research attention for solid-state lighting devices. In this paper, we report two air-stable zinc complexes, where the zinc is coordinated to two sterically encumbered ß-diketiminate ligands in a tetrahedral geometry. In such a geometry, eight phenyl/aryl rings from the ligand backbones are oriented in a propeller shape, augmenting the restricted rotation of the putative rings. Such an architecture harnesses aggregation-induced emission behavior with an excellent solid-state emission property. The rigidity of these molecules reduces the possibility of non-radiative transitions and makes them excellent fluorescence emitters. Both molecules exhibit electroluminescence (EL) in the yellowish-green region of the visible spectrum. We have utilized these molecules as emitters to fabricate multilayered organic light-emitting diode (OLED) devices. The emitter Zn-I in host m-MTDATA exhibits EL with a maximum external quantum efficiency of 4.4%. Among the handful of zinc-based OLEDs, the performance of this emitter is very commendable with power and current efficacies of 15.2 lm W-1 and 12.1 cd A-1, respectively, along with a brightness of 2426 cd m-2.