Ca2+ Regulates ERp57-Calnexin Complex Formation

ERp57, a member of the protein disulfide isomerase family, is a ubiquitous disulfide catalyst that functions in the oxidative folding of various clients in the mammalian endoplasmic reticulum (ER). In concert with ER lectin-like chaperones calnexin and calreticulin (CNX/CRT), ERp57 functions in virtually all folding stages from co-translation to post-translation, and thus plays a critical role in maintaining protein homeostasis, with direct implication for pathology. Here, we present mechanisms by which Ca2+ regulates the formation of the ERp57-calnexin complex. Biochemical and isothermal titration calorimetry analyses revealed that ERp57 strongly interacts with CNX via a non-covalent bond in the absence of Ca2+. The ERp57-CNX complex not only promoted the oxidative folding of human leukocyte antigen heavy chains, but also inhibited client aggregation. These results suggest that this complex performs both enzymatic and chaperoning functions under abnormal physiological conditions, such as Ca2+ depletion, to effectively guide proper oxidative protein folding. The findings shed light on the molecular mechanisms underpinning crosstalk between the chaperone network and Ca2+

Design guidelines for the SPICE parameters of waveform-selective metasurfaces varying with the incident pulse width at a constant oscillation frequency

In this study, we numerically demonstrate how the response of recently reported circuit-based metasurfaces is characterized by their circuit parameters. These metasurfaces, which include a set of four diodes as a full wave rectifier, are capable of sensing different waves even at the same frequency in response to the incident waveform, or more specifically the pulse width. This study reveals the relationship between the electromagnetic response of such waveform-selective metasurfaces and the SPICE parameters of the diodes used. First, we show that reducing a parasitic capacitive component of the diodes is important for realization of waveform-selective metasurfaces in a higher frequency regime. Second, we report that the operating power level is closely related to the saturation current and the breakdown voltage of the diodes. Moreover, the operating power range is found to be broadened by introducing an additional resistor into the inside of the diode bridge. Our study is expected to provide design guidelines for circuit-based waveform-selective metasurfaces to select/fabricate optimal diodes and enhance the waveform-selective performance at the target frequency and power level.Comment: 9 pages, 9 figure

Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding

The physiological functions of proteins are destined by their unique three-dimensional structures. Almost all biological kingdoms share conserved disulfide-catalysts and chaperone networks that assist in correct protein folding and prevent aggregation. Disruption of these networks is implicated in pathogenesis, including neurodegenerative disease. In the mammalian endoplasmic reticulum (ER), more than 20 members of the protein disulfide isomerase family (PDIs) are believed to cooperate in the client folding pathway, but it remains unclear whether complex formation among PDIs via non-covalent interaction is involved in regulating their enzymatic and chaperone functions. Herein, we report novel functional hetero complexes between PDIs that promote oxidative folding and inhibit aggregation along client folding. The findings provide insight into the physiological significance of disulfide-catalyst and chaperone networks and clues for understanding pathogenesis associated with disruption of the networks.P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured cells, but it remains unclear whether complex formation between P5 and other PDIs is involved in regulating enzymatic and chaperone functions. Herein, we established the far-western blot method to detect non-covalent interactions between P5 and other PDIs and found that PDI and ERp72 are partner proteins of P5. The enzymatic activity of P5-mediated oxidative folding is up-regulated by PDI, while the chaperone activity of P5 is stimulated by ERp72. These findings shed light on the mechanism by which the complex formations among PDIs drive to synergistically accelerate protein folding and prevents aggregation. This knowledge has implications for understanding misfolding-related pathology

Design and analysis for the SPICE parameters of waveform-selective metasurfaces varying with the incident pulse width at a constant oscillation frequency

Abstract In this study, we numerically demonstrate how the response of recently reported circuit-based metasurfaces is characterized by their circuit parameters. These metasurfaces, which include a set of four diodes as a full wave rectifier, are capable of sensing different waves even at the same frequency in response to the incident waveform, or more specifically the pulse width. This study reveals the relationship between the electromagnetic response of such waveform-selective metasurfaces and the SPICE parameters of the diodes used. In particular, we draw conclusions about how the SPICE parameters are related to (1) the high-frequency operation, (2) input power requirement and (3) dynamic range of waveform-selective metasurfaces with supporting simulation results. First, we show that reducing a parasitic capacitive component of the diodes is important for realization of the waveform-selective metasurfaces in a higher frequency regime. Second, we report that the operating power level is closely related to the saturation current and the breakdown voltage of the diodes. Moreover, the operating power range is found to be broadened by introducing an additional resistor into the inside of the diode bridge. Our study is expected to provide design guidelines for circuit-based waveform-selective metasurfaces to select/fabricate optimal diodes and enhance the waveform-selective performance at the target frequency and power level. Our results are usefully exploited to ensure the selectivity based on the pulse duration of the incident wave in a range of potential applications including electromagnetic interference, wireless power transfer, antenna design, wireless communications, and sensing