Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide 2′,5′ cGAMP that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription of the IFN-β gene. The structure of mouse cGAS bound to an 18 bp dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming a 2:2 complex. Enzyme assays and IFN-β reporter assays of cGAS mutants demonstrated that interactions at both DNA binding sites are essential for cGAS activation. Mutagenesis and DNA binding studies showed that the two sites bind dsDNA cooperatively and site B plays a critical role in DNA binding. The structure of mouse cGAS bound to dsDNA and 2′,5′ cGAMP provided insight into the catalytic mechanism of cGAS. These results demonstrated that cGAS is activated by dsDNA-induced oligomerization.
Crystal structure determination has revolutionized modern science in biology, chemistry, and physics. However, the difficulty in obtaining periodic crystal lattices which are needed for X-ray crystal analysis has hindered the determination of atomic structure in nanomaterials, known as the "nanostructure problem". Here, by using rigid and bulky ligands, we have overcome this limitation and successfully solved the X-ray crystallographic structure of the largest reported thiolated gold nanomolecule, Au133S52. The total composition, Au133(SPh-tBu)52, was verified using high resolution electrospray ionization mass spectrometry (ESI-MS). The experimental and simulated optical spectra show an emergent surface plasmon resonance that is more pronounced than in the slightly larger Au144(SCH2CH2Ph)60. Theoretical analysis indicates that the presence of rigid and bulky ligands is the key to the successful crystal formation.
Tailoring nanoarchitecture of materials offers unprecedented opportunities in utilization of their functional properties. Nanostructures of vanadium oxide, synthesized by electrochemical deposition, are studied as a cathode material for rechargeable Na-ion batteries. Ex situ and in situ synchrotron characterizations revealed the presence of an electrochemically responsive bilayered structure with adjustable intralayer spacing that accommodates intercalation of Na(+) ions. Sodium intake induces organization of overall structure with appearance of both long- and short-range order, while deintercalation is accompanied with the loss of long-range order, whereas short-range order is preserved. Nanostructured electrodes achieve theoretical reversible capacity for Na(2)V(2)O(5) stochiometry of 250 mAh/g. The stability evaluation during charge-discharge cycles at room temperature revealed an efficient 3 V cathode material with superb performance: energy density of ~760 Wh/kg and power density of 1200 W/kg. These results demonstrate feasibility of development of the ambient temperature Na-ion rechargeable batteries by employment of electrodes with tailored nanoarchitectures.
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