Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Here, using cryo-EM, biochemistry and cell biology, the authors reveal the unique assembly, catalytic mechanism, multimodal substrate recruitment and regulation of the atypical ubiquitin ligase complex CUL9–RBX1.
Precise protease positioning and gating of the proteasome core require the ordered assembly of 28 subunits. Cryo-EM structures of seven intermediates visualize five dedicated chaperones and three propeptides mediating step-by-step assembly of the human 20S proteasome.
To prevent promiscuous protein degradation, proteasomes are initially assembled as inactive complexes. Their activation is autocatalytic and coupled to assembly. Here the authors uncover key aspects of the autocatalytic activation mechanism.
The authors describe the structure of an adenylyl cyclase 5 and Gβγ complex, which potentially influences a neural signalling pathway modulating motor function. Mutations in the Gβγ binding site on AC5 are linked to heritable forms of dyskinesia.
The authors report the structures of human CHT1 in the outward-open, inward-occluded and inward-open states, reveal the mechanism of HC-3 inhibition and choline recognition and elucidate the regulatory role of the intracellular helix IH1.
Here the authors structurally characterize respiratory supercomplexes, revealing that, in addition to the known ‘canonical’ respirasome, mammalian mitochondria contain two novel respirasome types, one of which incorporates supercomplex assembly factor SCAF1.
Phosphoinositide 3-kinase γ plays critical roles in neutrophil chemotaxis and cancer metastasis. Here, using cryo-EM and functional studies, the authors reveal how two molecules of a key activator, Gβγ, bind to and alter the conformation of the enzyme.
Here, using cryo-EM, authors reveal that amyloid-β and tau are identical in Alzheimer disease and Down syndrome. This has implications for assessing whether adults with Down syndrome could be included in Alzheimer disease clinical trials.
Here, four cryo-EM structures of Mtb OppABCD reveal an assembly of a cluster C substrate-binding protein and its translocator, as well as the [4Fe–4S] cluster-regulated transport mechanism of oligopeptide permeases found in bacteria.
Precise protein synthesis is achieved by tRNA modifications. Here the authors revealed that modified cytidines in tRNAIle use their long side chains to make additional interactions with mRNA for stable tRNA binding on the ribosome.
Rybak and Gagnon elucidate the mechanism of AUG codon avoidance by the minor isoleucine tRNA in Escherichia coli. The lysidinylated C34 in the anticodon loop of tRNAIle weakens interactions with the mRNA and destabilizes the EF-Tu ternary complex.
Transcription of toxin–antitoxin modules is regulated by conditional cooperativity, where the toxin enables or disrupts antitoxin-driven repression. Here, the authors solve the structural basis for the conditional cooperativity of Salmonella TacAT3.
Examining artificial embryos (gastruloids), Merle et al. uncover precise gene organization and proportional growth, providing insights into fundamental principles of developmental processes in mammalian systems.
The DNA polymerase α–primase complex undergoes dramatic configurational rearrangements to synthesize chimeric RNA-DNA primers across two separate active sites while maintaining simultaneous interactions at opposite ends of the primer–template duplex.
Here, the authors determine the structure of the human outer kinetochore KMN network complex, showing that it forms an extended and rigid rod-like structure and that it exists in an auto-inhibited state which can be relieved by phosphorylation.
During cell division, kinetochores anchor chromosomes to spindle microtubules. Here, the authors report a comprehensive structure–function analysis of the kinetochore’s main microtubule receptor, the KMN network, shedding new light on its organization.
Here, the authors ask how much regulatory activity DNA is expected to have in the absence of selection. In yeast and humans, they find that gene regulatory activity is common in evolutionarily naive DNA, suggesting that activity is not always indicative of function.
JADE is a subunit of human acetyltransferase complex HBO1 that is essential in transcriptional regulation. Gaurav et al. characterize the molecular mechanism by which JADE mediates genomic association and enzymatic and pathological activities of the HBO1 complex.
A calcium ion binding site, hidden in the highly conserved gate of the synaptic AMPA-type ionotropic glutamate receptor, reveals upon gating and controls ion transport across the membrane, providing new mechanistic insights on ion permeation.