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Antibiotic tolerance, the capacity of genetically susceptible bacteria to survive the lethal effects of antibiotic treatment, plays a critical and underappreciated role in the disease burden of bacterial infections. Here, we take a pathogen-by-pathogen approach to illustrate the clinical significance of antibiotic tolerance and discuss how the physiology of specific pathogens in their infection environments...
Regulation of apoptosis by Bcl-2 family proteins is a paradigm for complex protein-protein and protein-membrane systems. Elucidating the molecular mechanisms of these interactions in vitro in live cells and in animal studies has been significantly enhanced by using fluorescence techniques.
In normal circumstances, the Bcl-2 family dutifully governs when cells die. However, the rules of engagement between the pro- and antiapoptotic family members are still contested, and how Bax is transformed from a cytosolic monomer to an outer mitochondrial membrane-permeabilizing oligomer is unclear. With fluorescence techniques and an in vitro system, the combination of tBid and Bax produced dramatic...
Plasma membrane wounds are repaired by a mechanism involving Ca 2+ -regulated exocytosis. Elevation in intracellular [Ca 2+ ] triggers fusion of lysosomes with the plasma membrane, a process regulated by the lysosomal synaptotagmin isoform Syt VII. Here, we show that Ca 2+ -regulated exocytosis of lysosomes is required for the repair of plasma membrane disruptions...
During the cotranslational integration of a nascent protein into the endoplasmic reticulum membrane, the transmembrane (TM) sequence moves out of an aqueous pore formed by Sec61α, TRAM, and other proteins and into the nonpolar lipid bilayer. Photocross-linking reveals that this movement involves the sequential passage of the TM domain through three different proteinaceous environments: one adjacent...
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