Inflammasomes are key signalling platforms that detect pathogenic microorganisms and sterile stressors, and that activate the highly pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. In ...this Review, we discuss the complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response, and we highlight the similarities to another molecular signalling platform - the apoptosome - that monitors cellular health. Extracellular regulatory mechanisms are discussed, as well as the intracellular control of inflammasome assembly, for example, via ion fluxes, free radicals and autophagy.
Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in ...melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.
Display omitted
► Electrostatic attraction underlies innate dsDNA recognition by the HIN domains ► Both OB folds and the linker between them engage the dsDNA backbone ► An autoinhibited state of AIM2 is activated by DNA that liberates the PYD domain ► DNA serves as an oligomerization platform for the inflammasome assembly
Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker ...histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures.
Display omitted
•Structure of the globular domain of linker histone H5 bound to the nucleosome•The globular domain interacts with the nucleosome dyad and both linker DNAs•Linker histones can recognize the nucleosome by on- or off-dyad binding mode•Different binding modes lead to distinct higher-order structures of chromatin
Zhou et al. determined the crystal structure of the globular domain of linker histone H5 bound to the nucleosome. The globular domain binds to the nucleosome dyad and interacts with both linker DNAs. They further showed linker histones with different binding modes could lead to distinct higher-order structures of chromatin.
Abstract
CMOS-based computing systems that employ the von Neumann architecture are relatively limited when it comes to parallel data storage and processing. In contrast, the human brain is a living ...computational signal processing unit that operates with extreme parallelism and energy efficiency. Although numerous neuromorphic electronic devices have emerged in the last decade, most of them are rigid or contain materials that are toxic to biological systems. In this work, we report on biocompatible bilayer graphene-based artificial synaptic transistors (BLAST) capable of mimicking synaptic behavior. The BLAST devices leverage a dry ion-selective membrane, enabling long-term potentiation, with ~50 aJ/µm
2
switching energy efficiency, at least an order of magnitude lower than previous reports on two-dimensional material-based artificial synapses. The devices show unique metaplasticity, a useful feature for generalizable deep neural networks, and we demonstrate that metaplastic BLASTs outperform ideal linear synapses in classic image classification tasks. With switching energy well below the 1 fJ energy estimated per biological synapse, the proposed devices are powerful candidates for bio-interfaced online learning, bridging the gap between artificial and biological neural networks.
Thermophotovoltaic power conversion utilizes thermal radiation from a local heat source to generate electricity in a photovoltaic cell. It was shown in recent years that the addition of a highly ...reflective rear mirror to a solar cell maximizes the extraction of luminescence. This, in turn, boosts the voltage, enabling the creation of record-breaking solar efficiency. Now we report that the rear mirror can be used to create thermophotovoltaic systems with unprecedented high thermophotovoltaic efficiency. This mirror reflects low-energy infrared photons back into the heat source, recovering their energy. Therefore, the rear mirror serves a dual function; boosting the voltage and reusing infrared thermal photons. This allows the possibility of a practical >50% efficient thermophotovoltaic system. Based on this reflective rear mirror concept, we report a thermophotovoltaic efficiency of 29.1 ± 0.4% at an emitter temperature of 1,207 °C.
The nucleotidyl transferase cGAS, its second-messenger product cGAMP, and the cGAMP sensor STING form the basic mechanism of DNA sensing in the cytoplasm of mammalian cells. Several new reports now ...uncover key structural features associated with DNA recognition by cGAS and the catalytic mechanisms of cGAMP generation. Concurrent studies also reveal unique phosphodiester linkages in endogenous cGAMP that distinguish it from microbial cGAMP and other cyclic dinucleotides. Together, these studies provide a new perspective on DNA recognition in the innate immune system.
Lead halide materials have seen a recent surge of interest from the photovoltaics community following the observation of surprisingly high photovoltaic performance, with optoelectronic properties ...similar to GaAs. This begs the question: What is the limit for the efficiency of these materials? It has been known that under 1-sun illumination the efficiency limit of crystalline silicon is ∼29%, despite the Shockley–Queisser (SQ) limit for its bandgap being ∼33%: the discrepancy is due to strong Auger recombination. In this article, we show that methyl ammonium lead iodide (MAPbI3) likewise has a larger than expected Auger coefficient. Auger nonradiative recombination decreases the theoretical external luminescence efficiency to ∼95% at open-circuit conditions. The Auger penalty is much reduced at the operating point where the carrier density is less, producing an oddly high fill factor of ∼90.4%. This compensates the Auger penalty and leads to a power conversion efficiency of 30.5%, close to ideal for the MAPbI3 bandgap.
The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as ...an intracellular DNA sensor that mediates the induction of interferon-β (IFN-β). IFI16 directly associated with IFN-β-inducing viral DNA motifs. STING, a critical mediator of IFN-β responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-κB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).
Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the ...centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.
PDF
