Structural analysis of the intracellular domain of (pro)renin receptor fused to maltose-binding protein

The (pro)renin receptor (PRR) is an important component of the renin-angiotensin system (RAS), which regulates blood pressure and cardiovascular function. The integral membrane protein PRR contains a large extracellular domain (∼310 amino acids), a single transmembrane domain (∼20 amino acids) and an intracellular domain (∼19 amino acids). Although short, the intracellular (IC) domain of the PRR has functionally important roles in a number of signal transduction pathways activated by (pro)renin binding. Meanwhile, together with the transmembrane domain and a small portion of the extracellular domain (∼30 amino acids), the IC domain is also involved in assembly of V₀ portion of the vacuolar proton-translocating ATPase (V-ATPase). To better understand structural and multifunctional roles of the PRR-IC, we report the crystal structure of the PRR-IC domain as maltose-binding protein (MBP) fusion proteins at 2.0 Å (maltose-free) and 2.15 Å (maltose-bound). In the two separate crystal forms having significantly different unit-cell dimensions and molecular packing, MBP–PRR-IC fusion protein was found to be a dimer, which is different with the natural monomer of native MBP. The PRR-IC domain appears as a relatively flexible loop and is responsible for the dimerization of MBP fusion protein. Residues in the PRR-IC domain, particularly two tyrosines, dominate the intermonomer interactions, suggesting a role for the PRR-IC domain in protein oligomerization.     

TgZFP2 is a novel zinc finger protein involved in coordinating mitosis and budding in Toxoplasma

Zinc finger proteins (ZFPs) are one of the most abundant groups of proteins with a wide range of molecular functions. We have characterised a Toxoplasma protein that we named TgZFP2, as it bears a zinc finger domain conserved in eukaryotes. However, this protein has little homology outside this region and contains no other conserved domain that could hint for a particular function. We thus investigated TgZFP2 function by generating a conditional mutant. We showed that depletion of TgZFP2 leads to a drastic arrest in the parasite cell cycle, and complementation assays demonstrated the zinc finger domain is essential for TgZFP2 function. More precisely, whereas replication of the nuclear material is initially essentially unaltered, daughter cell budding is seriously impaired: to a large extent newly formed buds fail to incorporate nuclear material. TgZFP2 is found at the basal complex in extracellular parasites and after invasion, but as the parasites progress into cell division, it relocalises to cytoplasmic punctate structures and, strikingly, accumulates in the pericentrosomal area at the onset of daughter cell elongation. Centrosomes have emerged as major coordinators of the budding and nuclear cycles in Toxoplasma, and our study identifies a novel and important component of this machinery.     

The Zn2+ and Ca2+‐binding S100B and S100A1 proteins: beyond the myths

The S100 genes encode a conserved group of 21 vertebrate‐specific EF‐hand calcium‐binding proteins. Since their discovery in 1965, S100 proteins have remained enigmatic in terms of their cellular functions. In this review, we summarize the calcium‐ and zinc‐binding properties of the dimeric S100B and S100A1 proteins and highlight data that shed new light on the extracellular and intracellular regulation and functions of S100B. We point out that S100B and S100A1 homodimers are not functionally interchangeable and that in a S100A1/S100B heterodimer, S100A1 acts as a negative regulator for the ability of S100B to bind Zn²⁺. The Ca²⁺ and Zn²⁺‐dependent interactions of S100B with a wide array of proteins form the basis of its activities and have led to the derivation of some initial rules for S100B recognition of protein targets. However, recent findings have strongly suggested that these rules need to be revisited. Here, we describe a new consensus S100B binding motif present in intracellular and extracellular vertebrate‐specific proteins and propose a new model for stable interactions of S100B dimers with full‐length target proteins. A chaperone‐associated function for intracellular S100B in adaptive cellular stress responses is also discussed. This review may help guide future studies on the functions of S100 proteins in general.     

Seizure‐induced impairment in neuronal ketogenesis: Role of zinc‐α2‐glycoprotein in mitochondria

Ketone bodies (KBs) were known to suppress seizure. Untraditionally, neurons were recently reported to utilize fatty acids and produce KBs, but the effect of seizure on neuronal ketogenesis has not been researched. Zinc‐α2‐glycoprotein (ZAG) was reported to suppress seizure via unclear mechanism. Interestingly, ZAG was involved in fatty acid β‐oxidation and thus may exert anti‐epileptic effect by promoting ketogenesis. However, this promotive effect of ZAG on neuronal ketogenesis has not been clarified. In this study, we performed immunoprecipitation and mass spectrometry to identify potential interaction partners with ZAG. The mechanisms of how ZAG translocated into mitochondria were determined by quantitative coimmunoprecipitation after treatment with apoptozole, a heat shock cognate protein 70 (HSC70) inhibitor. ZAG level was modulated by lentivirus in neurons or adeno‐associated virus in rat brains. Seizure models were induced by magnesium (Mg²⁺)‐free artificial cerebrospinal fluid in neurons or intraperitoneal injection of pentylenetetrazole kindling in rats. Ketogenesis was determined by cyclic thio‐NADH method in supernatant of neurons or brain homogenate. The effect of peroxisome proliferator–activated receptor γ (PPARγ) on ZAG expression was examined by Western blot, quantitative real‐time polymerase chain reaction (qRT‐PCR) and chromatin immunoprecipitation qRT‐PCR. We found that seizure induced ketogenesis deficiency via a ZAG‐dependent mechanism. ZAG entered mitochondria through a HSC70‐dependent mechanism, promoted ketogenesis by binding to four β‐subunits of long‐chain L‐3‐hydroxyacyl‐CoA dehydrogenase (HADHB) and alleviated ketogenesis impairment in a neuronal seizure model and pentylenetetrazole‐kindled epileptic rats. Additionally, PPARγ activation up‐regulated ZAG expression by binding to promoter region of AZGP1 gene and promoted ketogenesis through a ZAG‐dependent mechanism.     

Strategies for Dendrite‐Free Anode in Aqueous Rechargeable Zinc Ion Batteries

Ongoing interest is focused on aqueous zinc ion batteries (ZIBs) for mass‐production energy storage systems as a result of their affordability, safety, and high energy density. Ensuring the stability of the electrode/electrolyte interface is of particular importance for prolonging the cycling ability to meet the practical requirements of rechargeable batteries. Zinc anodes exhibit poor cycle life and low coulombic efficiency, stemming from the severe dendrite growth, and irreversible byproducts such as H₂ and inactive ZnO. Great efforts have recently been devoted to zinc anode protection for designing high‐performance ZIBs. However, the intrinsic origins of zinc plating/striping are poorly understood, which greatly delay its potential applications. Rather than focusing on battery metrics, this review delves deeply into the underlying science that triggers the deposition/dissolution of zinc ions. Furthermore, recent advances in modulating the zinc coordination environment, uniforming interfacial electric fields, and inducing zinc deposition are highlighted and summarized. Finally, perspectives and suggestions are provided for designing highly stable zinc anodes for the industrialization of the aqueous rechargeable ZIBs in the near future.     

2D Amorphous V2O5/Graphene Heterostructures for High‐Safety Aqueous Zn‐Ion Batteries with Unprecedented Capacity and Ultrahigh Rate Capability

Rechargeable aqueous zinc‐ion batteries (ZIBs) are appealing due to their high safety, zinc abundance, and low cost. However, developing suitable cathode materials remains a great challenge. Herein, a novel 2D heterostructure of ultrathin amorphous vanadium pentoxide uniformly grown on graphene (A‐V₂O₅/G) with a very short ion diffusion pathway, abundant active sites, high electrical conductivity, and exceptional structural stability, is demonstrated for highly reversible aqueous ZIBs (A‐V₂O₅/G‐ZIBs), coupling with unprecedented high capacity, rate capability, long‐term cyclability, and excellent safety. As a result, 2D A‐V₂O₅/G heterostructures for stacked ZIBs at 0.1 A g^?1 display an ultrahigh capacity of 489 mAh g^?1, outperforming all reported ZIBs, with an admirable rate capability of 123 mAh g^?1 even at 70 A g^?1. Furthermore, the new‐concept prototype planar miniaturized zinc‐ion microbatteries (A‐V₂O₅/G‐ZIMBs), demonstrate a high volumetric capacity of 20 mAh cm^?3 at 1 mA cm^?2, long cyclability; holding high capacity retention of 80% after 3500 cycles, and in‐series integration, demonstrative of great potential for highly‐safe microsized power sources. Therefore, the exploration of such 2D heterostructure materials with strong synergy is a reliable strategy for developing safe and high‐performance energy storage devices.     

Recent Advances in Vanadium‐Based Aqueous Rechargeable Zinc‐Ion Batteries

Aqueous zinc‐ion batteries (AZIBs) have attracted considerable attention as promising next‐generation power sources because of the abundance, low cost, eco‐friendliness, and high security of Zn resources. Recently, vanadium‐based materials as cathodes in AZIBs have gained interest owing to their rich electrochemical interaction with Zn²⁺ and high theoretical capacity. However, existing AZIBs are still far from meeting commercial requirements. This article summarizes recent advances in the rational design of vanadium‐based materials toward AZIBs. In particular, it highlights various tactics that have been reported to increase the intercalation space, structural stability, and the diffusion ability of the guest Zn²⁺, as well as explores the structure‐dependent electrochemical performance and the corresponding energy storage mechanism. Furthermore, this article summarizes recent achievements in the optimization of aqueous electrolytes and Zn anodes to resolve the issues that remain with Zn anodes, including dendrite formation, passivation, corrosion, and the low coulombic efficiency of plating/stripping. The rationalization of these research findings can guide further investigations in the design of cathode/anode materials and electrolytes for next‐generation AZIBs.     

Flexible Pseudocapacitive Electrochromics via Inkjet Printing of Additive‐Free Tungsten Oxide Nanocrystal Ink

Direct inkjet printing of functional inks is an emerging and promising technique for the fabrication of electrochemical energy storage devices. Electrochromic energy devices combine electrochromic and energy storage functions, providing a rising and burgeoning technology for next‐generation intelligent power sources. However, printing such devices has, in the past, required additives or other second phase materials in order to create inks with suitable rheological properties, which can lower printed device performance. Here, tungsten oxide nanocrystal inks are formulated without any additives for the printing of high‐quality tungsten oxide thin films. This allows the assembly of novel electrochromic pseudocapacitive zinc‐ion devices, which exhibit a relatively high capacity (≈260 C g^?1 at 1 A g^?1) with good cycling stability, a high coloration efficiency, and fast switching response. These results validate the promising features of inkjet‐printed electrochromic zinc‐ion energy storage devices in a wide range of applications in flexible electronic devices, energy‐saving buildings, and intelligent systems.     

Continuous capture of recombinant antibodies by ZnCl2 precipitation without polyethylene glycol

The capture of recombinant antibodies from cell culture broth is the first critical step of downstream processing. We were able to develop a precipitation‐based method for the capture and purification of monoclonal antibodies based on divalent cations, namely ZnCl₂. Traditional precipitation processes have to deal with high dilution factors especially for resolubilization and higher viscosity due to the use of PEG as precipitation or co‐precipitation agent. By the use of the crosslinking nature of divalent cations without the use of PEG, we kept viscosity from the supernatant and resolubilization dilution factors very low. This is especially beneficial for the solid–liquid separation for the harvest and wash of the precipitate in continuous mode. For this harvest and wash, we used tangential flow filtration that benefits a lot from low viscosity solutions, which minimizes the membrane fouling. With this precipitation based on ZnCl_2, we were able to implement a very lean and efficient process. We demonstrated precipitation studies with three different antibodies, Adalimumab, Trastuzumab, and Denosumab, and a continuous capture case study using tangential flow filtration for precipitate recovery. In this study, we achieved yields of 70%.     

Aus der Versuchsstation für Tierernährung,Perchtoldsdorf/Wien

This study aimed to compare the effects of organic (proteinate) and inorganic (sulphate) copper (Cu) and zinc (Zn) supplements, in presence or absence of a mannan oligosaccharide (MOS) supplement, on mineral solubility and digestibility in pigs. Twenty-eight barrows (25 ± 4 kg) assigned randomly to four treatment groups were fed a corn-wheat-soya bean meal diet with 10 mg/kg of Cu and 100 mg/kg of Zn supplied as organic or inorganic supplement, and supplemented or not with 0.1% MOS. After an adaptation period, total faeces and urine were collected for a period of 6–7 days. Pigs were then euthanatised and digesta from ileum and caecum were collected. Apparent digestibility was calculated in ileum and caecum using titanium dioxide. The organic mineral supplement improved total (faecal) digestibility and retained/ingested ratio of Cu (p < 0.05) while reducing apparent digestibility of Zn in the ileum (p < 0.05) without effect on total digestibility of Zn. Solubilities of Cu and Zn in liquid fraction of ileum and caecum were not affected by mineral sources. Although MOS supplement increased Cu solubility in the ileum (p < 0.05), it had no effect on digestibility of Zn and Cu in ileum, caecum and faeces, retained/ingested ratio of Zn and Cu, or pH and volatile fatty acid concentration in ileal and caecal digesta. In conclusion, organic mineral supplement improved total digestibility and retained/ingested ratio of Cu in pigs but this cannot be attributed to its solubility in ileal and caecal digesta. The MOS supplement did not interfere with digestibility or dietary utilisation of Zn and Cu in pigs fed above the Zn and Cu requirements.