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Holliday junction resolvases lock dynamic DNA four-way junctions into specific structural conformations for symmetric DNA cleavage. Single-molecule studies now reveal that resolvases can relax their grip, enabling Holliday junction conformer transitions and branch migration in the enzyme-bound form.
Single-molecule analysis reveals a novel binding state of Holliday junction (HJ) resolving enzymes where the enzymes partially dissociate from the HJ and allowing nearly unencumbered HJ dynamics, suggesting coupled branch migration and HJ resolution.
Assembly of the mycobacterial cell envelope layers, including peptidoglycan (PG) and the mycomembrane (MM), is synchronous during elongation, when a mobile fraction of the MM diffuses into the septum after thinning of the diffusion barrier formed by PG.
A collection of genetically encoded tools, each with their own capabilities, limitations and performance characteristics, are available for monitoring and manipulating neuronal activity that could allow visualizing the brain at single-cell resolution.
Faster-than-transcription control of cellular activities is an important but challenging engineering target. Using split ferredoxins and induced dimerization or conformational changes, newly developed metalloprotein switches provide a fast method to control electron flux.
Discovery and exploitation of inherent reaction features of chlorofluoroacetamide (CFA) as a warhead such as low off-target activity and reversible reactivity with cysteine enable specific covalent inhibition of targeted kinases.
A cell-based phenotypic screen identifying inhibitors of Notch signaling led to the discovery of NVS-ZP7-4, which blocks the activity of the zinc transporter SLC39a7 (ZIP7) and induces cell death through an ER stress mechanism.
Screening with a small-molecule reactive-oxygen-species generator identifies the serine hydrolase enzyme ABHD12 as a lipase for the proapoptotic oxidized phoshatidylserine (ox-PS) lipids, which trigger production of proinflammatory cytokines.
The reconstitution of gentamicin B biosynthesis reveals the existence of multiple new intermediates and branching pathways and enables the identification of factors that contribute to the low levels of the natural product in the native producer.
Live-cell imaging and virus trafficking studies show that the host innate immune receptor IFITM3 localizes with endocytic vesicles that fuse with incoming viruses to ultimately enhance their traffic to lysosomes.
Two protein circuit systems, split-protease-cleavable orthogonal coiled-coil logic (SPOC logic) and circuits of hacked orthogonal modular proteases (CHOMP), have been developed to permit rapid and logic function-based control of mammalian cellular signaling.
A chemoenzymatic tagging approach was developed and identified eukaryotic host proteins that are O-glycosylated by SetA from Legionella. The SetA-consensus motif was applied to recombinant proteins yielding a site-specific O-glucosylation method.
A combination of elicitor screening to induce expression of silent biosynthetic gene clusters with imaging mass spectrometry to visualize the resulting metabolome enables the discovery of nine cryptic natural products.