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Eubacteria inactivate their ribosomes as 100S dimers or 70S monomers upon entry into stationary phase. In Escherichia coli, 100S dimer formation is mediated by ribosome modulation factor (RMF) and hibernation promoting factor (HPF), or alternatively, the YfiA protein inactivates ribosomes as 70S monomers. Here, we present high-resolution crystal structures(More)
During peptide-bond formation on the ribosome, the α-amine of an aminoacyl-tRNA attacks the ester carbonyl carbon of a peptidyl-tRNA to yield a peptide lengthened by one amino acid. Although the ribosome's contribution to catalysis is predominantly entropic, the lack of high-resolution structural data for the complete active site in complex with full-length(More)
Enhancers are regulatory DNA sequences that activate transcription over long distances. Recent studies revealed a widespread role of distant activation in eukaryotic gene regulation and in development of various human diseases, including cancer. Genomic and gene-targeted studies of enhancer action revealed novel mechanisms of transcriptional activation over(More)
Nucleosomes uniquely positioned on high-affinity DNA sequences present a polar barrier to transcription by human and yeast RNA polymerase II (Pol II). In one transcriptional orientation, these nucleosomes provide a strong, factor- and salt-insensitive barrier at the entry into the H3/H4 tetramer that can be recapitulated without H2A/H2B dimers. The same(More)
Numerous DNA transactions in eukaryotic nuclei are regulated by elements (enhancers) that can directly interact with their targets over large regions of DNA organized into chromatin. The mechanisms allowing communication over a distance in chromatin are unknown. We have established an experimental system allowing quantitative analysis of the impact of(More)
The structures of ribosomes in complex with inhibitors of translation have not only shed light on the interactions of antibiotics with the ribosome but also on the underlying mechanisms by which they interfere with the ribosome function. Several recent papers [1(•),2(••),3,4] have correlated the available ribosome structures with the wealth of biochemical(More)
Action across long distances on chromatin is a hallmark of eukaryotic transcriptional regulation. Although chromatin structure per se can support long-range interactions, the mechanisms of efficient communication between widely spaced DNA modules in chromatin remain a mystery. The molecular simulations described herein suggest that transient binary(More)
Regulation of many biological processes in eukaryotes involves distant communication between the regulatory DNA sequences (e.g., enhancers) and their targets over the DNA regions organized in chromatin. However previously developed methods for analysis of communication in chromatin in vitro are artifact-prone and/or do not allow analysis of communication on(More)
Regulation of many biological processes often occurs by DNA sequences positioned over a large distance from the site of action. Such sequences, capable of activating transcription over a distance, are termed enhancers. Several experimental approaches for analysis of the mechanisms of communication over a distance between DNA regions positioned on the same(More)
The translocation of mRNA and tRNA through the ribosome is catalyzed by elongation factor G (EF-G), a universally conserved guanosine triphosphate hydrolase (GTPase). The mechanism by which the closely related decapeptide antibiotics dityromycin and GE82832 inhibit EF-G-catalyzed translocation is elucidated in this study. Using crystallographic and(More)