Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.
Nucleic acids from bacteria or viruses induce potent immune responses in infected cells1–4. The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses5,6. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor7,8. It catalyzes the synthesis of cyclic GMP-AMP (cGAMP)9–12, which stimulates the induction of type I interferons (IFN-Is) through the STING-TBK1-IRF-3 signaling axis13–15. Stimulator of interferon genes (STING) oligomerizes upon cGAMP binding, leading to the recruitment and activation of tank-binding kinase 1 (TBK1)8,16. Interferon regulatory factor 3 (IRF-3) is then recruited to the signaling complex and activated by TBK18,17–20. Phosphorylated IRF-3 translocates to the nucleus and initiates the expression of IFN-Is21. However, the precise mechanisms governing STING activation by cGAMP and subsequent TBK1 activation by STING remained poorly understood. Here we show that a conserved PLPLRT/SD motif within the C-terminal tail of STING mediates the recruitment and activation of TBK1. Crystal structures of TBK1 bound to STING reveal that the PLPLRT/SD motif binds to the dimer interface of TBK1. Cell-based studies confirm that the direct interaction between TBK1 and STING is essential for IFN-β induction upon cGAMP stimulation. Moreover, we show that full-length STING oligomerizes upon cGAMP binding and highlight this as an essential step in the activation of STING-mediated signaling.
Nature's highly efficient light-harvesting antennae, such as those found in green sulfur bacteria, consist of supramolecular building blocks that self-assemble into a hierarchy of close-packed structures. In an effort to mimic the fundamental processes that govern nature's efficient systems, it is important to elucidate the role of each level of hierarchy: from molecule, to supramolecular building block, to close-packed building blocks. Here, we study the impact of hierarchical structure. We present a model system that mirrors nature's complexity: cylinders self-assembled from cyanine-dye molecules. Our work reveals that even though close-packing may alter the cylinders' soft mesoscopic structure, robust delocalized excitons are retained: Internal order and strong excitation-transfer interactions-prerequisites for efficient energy transport-are both maintained. Our results suggest that the cylindrical geometry strongly favors robust excitons; it presents a rational design that is potentially key to nature's high efficiency, allowing construction of efficient lightharvesting devices even from soft, supramolecular materials. supramolecular assembly | self-assembled excitonic nanoscale systems | photosynthesis | exciton theory | light-harvesting antennae systems T he most remarkable materials that demonstrate the ability to capture solar energy are natural photosynthetic systems such as those found in primitive marine algae and bacteria (1-10). Their light-harvesting (LH) antennae are crucial components, because they absorb the light and direct the resulting excitation energy efficiently to a reaction center, which then converts these excitations (excitons) into charge-separated states (1,4,11,12). Although the noncovalent interactions that link the individual molecules within the LH antennae are weak, the excitation transfer interactions between the molecules are relatively strong; new excited states, so-called Frenkel excitons (13), are generated that are delocalized over a number of molecules (1). These delocalized excitons are key to nature's efficiency and are therefore of high interest (14)(15)(16)(17)(18)(19)(20).To create such efficient LH systems, nature assembles molecular subunits into individual supramolecular structures, which are then further assembled into close-packed superstructures (1, 4, 7-10, 12, 21). This hierarchical assembly is a generic motif of nature's photosynthetic systems. As with natural systems, assembling artificial LH devices from supramolecular structures will require close packing into hierarchical assemblies to maximize the amount of absorbed light (19). Therefore, key to our ability to tune materials properties for efficient LH applications is a basic understanding of the role of each level of the hierarchy: from the individual molecule, to the individual supramolecular building block, to the close-packed assembly. Whereas the role of the individual molecules in the excitonic properties of the building blocks is well-studied (1, 7-10, 20, 22-37), the effect of structural hierar...
The axoneme forms the essential and conserved core of cilia and flagella. We have used cryo-electron tomography of Chlamydomonas and sea urchin flagella to answer long-standing questions and to provide information about the structure of axonemal doublet microtubules (DMTs). Solving an ongoing controversy, we show that B-tubules of DMTs contain exactly 10 protofilaments (PFs) and that the inner junction (IJ) and outer junction between the A-and B-tubules are fundamentally different. The outer junction, crucial for the initiation of doublet formation, appears to be formed by close interactions between the tubulin subunits of three PFs with unusual tubulin interfaces; other investigators have reported that this junction is weakened by mutations affecting posttranslational modifications of tubulin. The IJ consists of an axially periodic ladder-like structure connecting tubulin PFs of the A-and B-tubules. The recently discovered microtubule inner proteins (MIPs) on the inside of the A-and B-tubules are more complex than previously thought. They are composed of alternating small and large subunits with periodicities of 16 and/or 48 nm. MIP3 forms arches connecting B-tubule PFs, contrary to an earlier report that MIP3 forms the IJ. Finally, the "beak" structures within the B-tubules of Chlamydomonas DMT1, DMT5, and DMT6 are clearly composed of a longitudinal band of proteins repeating with a periodicity of 16 nm. These findings, discussed in relation to genetic and biochemical data, provide a critical foundation for future work on the molecular assembly and stability of the axoneme, as well as its function in motility and sensory transduction.microtubule stability | cilia | axoneme | ciliopathies | cytoskeleton
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