|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
The pathogenesis of the nerve paralysis induced by botulinum neurotoxins begins with their specific and high-affinity binding to peripheral nerve terminals. The new crystal structure of the toxin bound to its glycosylated receptor, presented in this issue, represents a major step forward in the understanding of how botulinum neurotoxin type A1, the toxin used in human therapy and cosmetics, binds its protein receptor.
Contrary to conventional wisdom that molecular chaperones rely on hydrophobic interactions to bind a wide variety of client proteins in danger of misfolding, three recent studies reveal that the ATP-independent chaperone Spy exploits electrostatic interactions to bind its clients quickly, yet loosely enough to enable folding of the client while it is chaperone bound.
This Perspective discusses how two complementary approaches, bottom-up in vitro and top-down in situ structural biology, have now converged to generate the first predictive structural models of the nuclear pore scaffold.
The lncRNA lnc-β-Catm associates with β-catenin and the methyltransferase Ezh2, thereby promoting β-catenin methylation and stabilization, which in turn lead to activation of Wnt–β-catenin signaling and promote liver CSCs self-renewal.
A new 'metal mimic' mutagenesis approach that captures a T5 flap endonuclease complex with an intact DNA substrate provides structural evidence that the single-stranded 5′ flap generated by Okazaki-fragment synthesis threads through the flap endonuclease enzyme.
The E3 ubiquitin ligase activity of the BRCA1–BARD1 complex is required to reposition 53BP1 on damaged chromatin and to promote DNA resection and repair via homologous recombination, in a mechanism involving the chromatin remodeler SMARCAD1.
BoNT/A1 invades motoneurons by binding to the neuronal receptor SV2. A combination of structural, biophysical and cellular analyses reveal that BoNT/A1 binding and uptake require glycosylation of SV2.
The canonical transcription factor ERG promotes degradation of a subset of mRNAs linked to mitotic progression by recruiting the CCR4–NOT deadenylation complex, thus revealing a new regulatory interplay between mRNA synthesis and degradation.
The histone methyltransferase DOT1L and the chromatin reader BRD4 together facilitate transcription of genes critical to the molecular pathogenesis of MLL leukemia.
Proteomic and genomic analysis of Polycomb group complexes in embryonic stem cells and neural progenitor cells identifies new PRC1 and PRC2 interaction partners and targets during neural lineage commitment.
READ is a new crystallographic approach to visualize conformational ensembles of heterogeneous and dynamic molecules. READ is applied here to structurally characterize the various folding states of client Im7 bound to chaperone Spy.
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.