Considerable attention has recently been paid to the N-Myc downstream-regulated gene (NDRG) family because of its potential as a tumor suppressor in many human cancers. Primary amino acid sequence information suggests that the NDRG family proteins may belong to the α/β-hydrolase (ABH) superfamily; however, their functional role has not yet been determined. Here, we present the crystal structures of the human and mouse NDRG2 proteins determined at 2.0 and 1.7 Å resolution, respectively. Both NDRG2 proteins show remarkable structural similarity to the ABH superfamily, despite limited sequence similarity. Structural analysis suggests that NDRG2 is a nonenzymatic member of the ABH superfamily, because it lacks the catalytic signature residues and has an occluded substrate-binding site. Several conserved structural features suggest NDRG may be involved in molecular interactions. Mutagenesis data based on the structural analysis support a crucial role for helix α6 in the suppression of TCF/β-catenin signaling in the tumorigenesis of human colorectal cancer, via a molecular interaction.
A new strategy is reported to achieve high-mobility, low-off-current, and operationally stable solution-processable metal-oxide thin-film transistors (TFTs) using a corrugated heterojunction channel structure. The corrugated heterojunction channel, having alternating thin-indium-tin-zinc-oxide (ITZO)/indium-gallium-zinc-oxide (IGZO) and thick-ITZO/IGZO film regions, enables the accumulated electron concentration to be tuned in the TFT off- and on-states via charge modulation at the vertical regions of the heterojunction. The ITZO/IGZO TFTs with optimized corrugated structure exhibit a maximum field-effect mobility >50 cm V s with an on/off current ratio of >10 and good operational stability (threshold voltage shift <1 V for a positive-gate-bias stress of 10 ks, without passivation). To exploit the underlying conduction mechanism of the corrugated heterojunction TFTs, a physical model is implemented by using a variety of chemical, structural, and electrical characterization tools and Technology Computer-Aided Design simulations. The physical model reveals that efficient charge manipulation is possible via the corrugated structure, by inducing an extremely high carrier concentration at the nanoscale vertical channel regions, enabling low off-currents and high on-currents depending on the applied gate bias.
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