These findings demonstrate that excess SFAs cause intracellular crystallization and subsequent lysosomal dysfunction, leading to the activation of the NLRP3 inflammasome, and provide novel insights into the pathogenesis of metabolic diseases.
The photoactivated adenylate cyclase (PAC) from the photosynthetic cyanobacterium Oscillatoria acuminata (OaPAC) detects light through a flavin chromophore within the N-terminal BLUF domain. BLUF domains have been found in a number of different light-activated proteins, but with different relative orientations. The two BLUF domains of OaPAC are found in close contact with each other, forming a coiled coil at their interface. Crystallization does not impede the activity switching of the enzyme, but flash cooling the crystals to cryogenic temperatures prevents the signature spectral changes that occur on photoactivation/deactivation. High-resolution crystallographic analysis of OaPAC in the fully activated state has been achieved by cryocooling the crystals immediately after light exposure. Comparison of the isomorphous light-and dark-state structures shows that the active site undergoes minimal changes, yet enzyme activity may increase up to 50-fold, depending on conditions. The OaPAC models will assist the development of simple, direct means to raise the cyclic AMP levels of living cells by light, and other tools for optogenetics.cAMP | BLUF domain | optogenetics | photoactivation | allostery
An adamantane-linked tetracene dyad (Tc-Ad-Tc) undergoes exergonic intramolecular singlet fission (SF), producing longlived (t = 175 µs) and high-energy (2 ´ 1.03 eV) multiexciton. Time-resolved absorption, fluorescence decay, and electron paramagnetic resonance (EPR) spectroscopic analysis revealed that the long-lived triplet species is generated in this system via correlated triplet pair having singlet and quintet characteristics. Time-resolved EPR analysis revealed formation of syn-and anti-conformers in the quintet, i.e. 5 ( 3 Tc-Ad-3 Tc)*. The quintet generation requires small conformational motion to induce singlet-quintet spin relaxation. The presence of aliphatic linkages, like the rigid adamantane group, may enable effective conservation of intrinsic high S1 and T1 levels of the original monomers, moderate bridge-mediated s-p interaction leading to exergonic intramolecular SF involving 1 Tc*-Ad-Tc ® 1 ( 3 Tc-Ad-3 Tc)*, and prevention of undesirable triplet-triplet annihilation, finally result in long-lived and high-energy multiexciton.
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