|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
Unrestrained 53BP1 activity causes fusions of dysfunctional telomeres and embryonic lethality associated with misrepair of DNA double-strand breaks in BRCA1-deficient mice. However, the physiological role of 53BP1 remains unclear, because it presumably did not evolve to carry out these pathological functions. A new report proposes that 53BP1 activity prevents hyper-resection and thereby promotes error-free DNA repair while suppressing alternative mutagenic pathways.
Mutations in the BRCA1 and BRCA2 genes strongly predispose carriers to breast and ovarian cancers. Two new studies reveal that FANCD2, a key component of the Fanconi anemia pathway, is essential for the survival of cells with BRCA1 or BRCA2 mutations. These findings pave the way for new 'synthetic lethal' strategies to kill BRCA-mutated cancers.
Ribosome profiling provides a snapshot of the mRNA positions of all elongating ribosomes in the cell. A new powerful enhancement of the technique, translation complex profile sequencing (TCP–seq), extends this mapping to scanning ribosomal complexes. In addition to its usefulness as a tool for studying the regulation of translation initiation, TCP–seq provides specific and powerful signatures of bona fide translation.
The crystal structure of the putative exonuclease Exuperantia, required for Drosophila anterior patterning, reveals an EXO-SAM-like domain architecture that is catalytically inactive but mediates dimerization and RNA binding, which are essential for bicoid localization.
A new study reveals that 53BP1 influences high-fidelity homology-directed repair by showing that its depletion in the presence of increasing DNA-damage levels triggers a shift from RAD51-dependent gene conversion, an error-free process, to RAD52-mediated single-strand annealing, which is mutagenic.
Structural and functional analysis of the Swi2/Snf2 remodeler demonstrates that the catalytic core of the protein is a competent remodeling machine, which rests in an inactive conformation poised for activation.
Biochemical, structural and cell-based analyses reveal a chaperone-like function of glycyl-tRNA synthetase, which supports neddylation via direct interactions with NEDD8, E1 and E2.
Solid-state NMR analyses reveal that the free backbone carbonyl groups associated with proline residues in the transmembrane helices play a key role in mediating rhodopsin activation.
EPR spectroscopy analyses elucidate how lipids affect the conformational dynamics of a multidrug secondary transporter, LmrP, and indicate a key role of the lipid headgroups in shaping the conformational-energy landscape of the transporter.
A crystal structure of the Zika virus NS3 RNA helicase reveals similarities to the RNA helicase from Dengue virus, with variability in loops typically involved in binding ATP and RNA, and aids in identification of potentially druggable hotspots.
Probing the synthetic lethal effect of FANCD2 deletion in BRCA2-deficient cells reveals independent roles of FANCD2 and BRCA2 in stabilizing stalled replication forks to maintain genome stability and promote cell survival.
The complete architecture of the yeast COG tethering complex is revealed by negative-stain electron microscopy, showing an intricate shape with up to five flexible legs.
Electron microscopy analyses of tethering complexes from different families, GARP and HOPS, show that they share a similar architecture featuring long flexible legs. The findings suggest that multisubunit tethering complexes use related structural frameworks to accomplish their functions.
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
The solution structure of the J-K region of the EMCV IRES establishes a preorganized recognition mode for hijacking translation initiation factor 4G.
Structural and functional analyses of HopZ1a, a member of the YopJ family of bacterial type III–secreted effectors, reveal the structural basis of YopJ effectors’ noncanonical acetyltransferase activity and allosteric regulation by inositol hexakisphosphate.
Cryo-EM and tomography imaging of influenza virus fusion with target membranes reveal structural intermediates of HA surface glycoprotein and their interactions with membranes as well as ultrastructural changes in the virus that accompany membrane fusion.
Analyses in supported lipid bilayers and in cells shed light on the roles of multiple SOS-membrane interactions in SOS's membrane recruitment and association, processive activation of Ras and signal attenuation.
An interactive structure-based approach was used to improve a vaccine antigen against respiratory syncytium virus (RSV), thus leading to immunogens with higher stability that elicit higher neutralizing titers in mice.
Light-scattering kinetics and atomic force and electron microscopy analyses show that Hsp70-mediated disassembly of clathrin cages occurs via a collision-pressure mechanism consistent with the entropic pulling model.
A cryo-EM structure of yeast AAA+ protein disaggregase Hsp104 with AMP-PNP reveals a spiral arrangement of the protomers and a continuous path for polypeptide translocation that explains Hsp104's processivity mechanism during disaggregation.
The inability of A-form RNA to form Hoogsteen base pairs provides a mechanism for how post-transcriptional modifications can disrupt RNA structure and might help explain why DNA is the molecular choice for storing genetic information.
The eukaryotic Elongator complex participates in modification of uridines in tRNAs. Structural and functional work on a bacterial Elp3, the catalytic subunit of Elongator, provides insight into the function and mechanism of this important enzyme.
Mass spectrometry, kinetics studies and in silico analyses indicate that multiple copies of the Skp chaperone are required for sequestration of 16-stranded or larger OMPs and prevention of their aggregation.
A cryo-EM structure of the human 26S proteasome in a resting state at an average resolution of 3.5Å reveals details in the interactions between subunits. An additional structure of the proteasome with USP14 bound suggests a mechanism for its activation.
The crystal structure of full-length NS1 protein from Zika virus reveals an extended surface for membrane association and a highly variable polar surface.
The crystal structure of the phage anti-CRISPR protein AcrF3 in complex with Cas3 reveals its mode of inhibition of the CRISPR–Cas bacterial immune system.