|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
After being used in the 1950s to treat morning sickness in pregnant women, with devastating effects, thalidomide and its derivatives (lenalidomide and pomalidomide) are now widely used in cancer therapy. New structural work from two groups gives insights into the basis for the teratogenicity and other clinical effects of these drugs.
Fluorescent probes at the exit channel and near the active site of RNA polymerase shed light on how transcriptional pausing is regulated.
Recent structural progress on prokaryotic and eukaryotic Argonaute proteins is reviewed here, along with the insights obtained into guide and target binding and target cleavage. Comprehensive phylogenetic analyses lead to a map of Argonaute's evolutionary paths, relating structural features and physiological roles.
Replication of Nipah virus, which causes human encephalitis, requires delivery of viral nucleoprotein N to the viral genome by phosphoprotein chaperone, P. The crystal structure of the N0–P core complex now reveals how the chaperone prevents premature N assembly on RNA and identifies a potential target for antiviral drugs.
Cancer cells lacking telomerase maintain telomere lengths required for cell growth through a recombination mechanism called ALT. Now, ALT-specific nuclear receptors are shown to recruit a zinc-finger protein that directs the nucleosome remodeler and histone deacetylase NuRD to telomeres to enhance homologous recombination.
Type I CRISPR-Cas systems require a target-searching Cascade complex and the Cas3 degradation machine to drive prokaryotic adaptation to alien nucleic acids. Cas3 crystal structures now reveal the mechanism of concerted DNA unwinding and degradation.
Alternative pre-mRNA splicing is often jointly controlled by multiple splicing factors. Here Muto and colleagues elucidate the structural basis for cooperative RNA recognition by two splicing regulators required for tissue-specific expression of C. elegans FGFR.
High-resolution structures of the 70S ribosome from Thermus thermophilus reveal a network of ordered waters in the peptidyl transferase center that suggests a mechanism for proton movement and formation and breakdown of the tetrahedral intermediate.
A combination of fluorescence and cross-linking assays are used to elucidate the reciprocal effects of RNA polymerase pausing and the secondary structure of the nascent transcript as it emerges from the translocating enzyme's RNA-exit channel.
The protein Cereblon, part of an ubiquitin E3 ligase complex, is the target for anticancer thalidomide analogs. The crystal structure of human Cereblon-DDB1 with bound lenalidomide reveals how the drug affects E3 substrate recruitment.
Chemical cross-linking MS and supporting biochemical and genetic analyses reveal the architecture of the yeast Core Factor complex and suggest how it directs transcription of RNA Pol I at rDNA promoters.
EF-G catalyzes translocation of tRNA–mRNA in the ribosome. Biochemical and structural analyses of EF-G indicate that EF-G disrupts interactions between the decoding center and the codon–anticodon duplex that constitute the barrier for translocation.
The precursor for miRNA-151 is found to compete with mature forms for target sites on E2f6 mRNA but not on a different mRNA. These findings indicate that miRNA processing can affect individual mRNA targets differently.
A systematic analysis reveals features of proteins synthesized at distal locations owing to mRNA localization, including the presence of intrinsically disordered segments and assembly-promoting modules. These findings suggest that asymmetric protein distribution enhances interaction fidelity.
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
Chemotherapeutic drug Gleevec (imatinib) is a potent and specific inhibitor of Abl kinase. NMR and fast kinetic analyses now reveal that Abl undergoes an induced-fit conformational change upon Gleevec binding.
A solution NMR structure of the pre-mRNA retention and splicing (RES) core complex from budding yeast now reveals how the trimer stabilizes the RRM of its Snu17 subunit to promote pre-mRNA interactions within the spliceosome.
A combination of two-dimensional gel electrophoresis and EM is used to isolate and characterize multiple template-switching intermediates generated in budding yeast during replication of damaged DNA.
New single-molecule imaging analyses reveal how dynamic interactions of RPA, Rad52 and Rad51 on single-stranded DNA direct assembly of the presynaptic complex that promotes strand invasion during homologous recombination.
A single-molecule optical-trapping approach is used to examine protein unfolding and translocation by double-ring AAA+ machine ClpA. Although ClpA can unfold some substrates faster than ClpX can, it translocates the unfolded polypeptide more slowly.
The protein TRIM28 is identified as a factor that modulates RNA polymerase II pausing and transcriptional elongation at a large number of mammalian genes. This function is regulated by transcription-coupled phosphorylation of TRIM28 at Ser824.
The crystal structure of a human cohesin subcomplex, SA2–Scc1, guides mutagenesis analyses to dissect the antagonistic roles of shugoshin and Wapl in regulating centromeric functions during mitosis.
Analyses of transcription and chromatin states during the yeast metabolic cycle reveal the links between different chromatin modifications and gene expression. The data also show that chromatin-modifier occupancies do not precisely match modification patterns.
High-resolution MS identifies ggt;4,300 SUMOylation sites in ggt;1,600 proteins in human cells under standard growth conditions and after proteasome inhibition or heat shock. The data reveal cross-talk between SUMO and other post-translational modifications.
Using the M2 stem-loop region to tag 16S pre-rRNA allows one-step isolation of assembly intermediates of the small ribosomal subunit from wild-type Escherichia coli. Characterization of these RNPs reveals multiple independent pathways for rRNA maturation.