Publications by authors named "Vanessa J Flegler"

Osmotically varying environments are challenging for bacterial cells. Sudden drops in osmolytes cause an increased membrane tension and rupture the cells in the absence of protective mechanisms. One family of protective proteins are mechanosensitive channels of small conductance that open in response to membrane tension.

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Lymphostatin is a key virulence factor of enteropathogenic and enterohaemorrhagic Escherichia coli, playing roles in bacterial colonisation of the gut and in the inhibition of lymphocyte proliferation and proinflammatory responses. The protein's glycosyltransferase and cysteine protease motifs are required for activity against lymphocytes, but high-resolution structural information has proven elusive. Here, we describe the structure of lymphostatin from enteropathogenic E.

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The ability to cope with and adapt to changes in the environment is essential for all organisms. Osmotic pressure is a universal threat when environmental changes result in an imbalance of osmolytes inside and outside the cell which causes a deviation from the normal turgor. Cells have developed a potent system to deal with this stress in the form of mechanosensitive ion channels.

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Article Synopsis
  • MscS is a mechanosensitive channel in bacteria that protects against hypoosmotic shock by sensing membrane tension and releasing solutes when internal pressure rises.
  • A key aspect of its function involves the interaction between lipids and sensor paddles, where lipids can detach from the membrane and move into hydrophobic pockets.
  • Research shows that MscS opens when lipids are removed using detergents, supporting the idea that lipid extrusion triggers the channel's opening and closing processes.
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The bacterial mechanosensitive channel of small conductance (MscS) is a well-studied model of how mechanical forces from the membrane can be sensed by an embedded protein. A recent study by Zhang et al. visualizes how MscS behaves under membrane tension, entering a desensitized state when it loses all coordinated lipids.

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The mechanosensitive channel of small conductance (MscS) is the prototype of an evolutionarily diversified large family that fine-tunes osmoregulation but is likely to fulfill additional functions. has six osmoprotective paralogs with different numbers of transmembrane helices. These helices are important for gating and sensing in MscS but the role of the additional helices in the paralogs is not understood.

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Article Synopsis
  • Polymeric micelles consist of a hydrophobic core for drug storage and a hydrophilic corona that stabilizes and solubilizes the structure in water.
  • Most research has focused on optimizing the hydrophobic block for better drug loading, while the hydrophilic block's influence, particularly using poly(ethylene glycol) (PEG) as a standard, has been overlooked.
  • A study using different poly(2-oxazoline)s and poly(2-oxazine)s shows that the type of hydrophilic block significantly affects the drug loading capacity of the micelles, emphasizing the need to consider the hydrophilic corona in the design of drug delivery systems.
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Since life has emerged, gradients of osmolytes over the cell membrane cause pressure changes in the cell and require tight regulation to prevent cell rupture. The mechanosensitive channel of small conductance (MscS) releases solutes and water when a hypo-osmotic shock raises the pressure in the cell. It is a member of a large family of MscS-like channels found in bacteria, archaea, fungi and plants and model for mechanosensation.

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Direct electron detectors are an essential asset for the resolution revolution in electron cryo microscopy of biological objects. The direct detectors provide two modes of data acquisition; the counting mode in which single electrons are counted, and the integrating mode in which the signal that arises from the incident electrons is integrated. While counting mode leads to far higher detective quantum efficiency at all spatial frequencies, the integrating mode enables faster data acquisition at higher exposure rates.

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