Transcriptional mechanisms that underlie dose-dependent modulation of gene expression in plant development have not been discovered, but cell-fate specification is known to rely heavily on positional cues ( 2). Various mechanisms have been proposed to explain dose-dependent transcriptional regulation mediated by morphogen gradients in animal development ( 1). The concentration-dependent transcriptional discrimination provides a mechanistic framework to explain the regulation of CLV3 levels that is critical for stem cell homeostasis. By deleting cis elements, manipulating the WUS-binding affinity and the homodimerization threshold of cis elements, and manipulating WUS levels, we show that the same cis elements mediate both the activation and repression of CLV3 at lower and higher WUS levels, respectively.
Here we show that WUS binds a group of cis-elements, cis- regulatory module, in the CLV3-regulatory region, with different affinities and conformations, consisting of monomers at lower concentration and as dimers at a higher level. How WUS regulates CLV3 levels has not been understood. In Arabidopsis shoot apical meristems, WUSCHEL (WUS), a stem cell-promoting transcription factor, accumulates at a higher level in the rib meristem and at a lower level in the central zone where it activates its own negative regulator, CLAVATA3 ( CLV3). However, the mechanisms of dose-dependent transcriptional regulation in plant development have not been understood. These investigations provide new insights into daptomycin’s phospholipid specificity and calcium binding behavior.Transcriptional mechanisms that underlie the dose-dependent regulation of gene expression in animal development have been studied extensively. Furthermore, unlike other calcium-dependent lipopeptide antibiotics, calcium binding by daptomycin is strongly dependent on the presence of phosphatidylglycerol. Our studies reveal that daptomycin shows a clear preference for the phosphoglycerol headgroup. In this study, we use isothermal titration calorimetry to further characterize the structural features of the target bacterial phospholipids that drive daptomycin binding. Daptomycin, the only clinically used calcium-dependent lipopeptide antibiotic, selectively disrupts Gram-positive bacterial membranes to illicit its bactericidal effect.
A molecular level understanding of the mechanism of action of antimicrobials plays a key role in developing new agents to combat the threat of antimicrobial resistance. Multidrug-resistant bacteria pose a serious global health threat as antibiotics are increasingly losing their clinical efficacy.
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