Research articles

Using cryo-electron tomography, Dendooven et al. determined the structure of the native budding yeast γ-tubulin ring complex (γTuRC) capping spindle microtubules and showed that γTuRC adopts an active closed conformation to function as a perfect geometric template for microtubule nucleation.

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 tRNA^Ile 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 tRNA^Ile 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.

Cryo-EM studies reveal that RYBP–PRC1 uses two distinct interfaces for binding unmodified and H2Aub1-modified nucleosomes. These binding modes enable the complex to generate H2Aub1 chromatin domains by a read–write mechanism.

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.

The biogenesis and recycling of the ‘heart’ of the human spliceosome, the U5 small nuclear ribonucleoprotein (snRNP), requires CD2BP2 and TSSC4. Here the authors present cryo-electron microscopy structures that reveal how these protein chaperones orchestrate the ATP-independent (re)generation of the U5 snRNP.

Here the authors report the structure of the human 20S U5 snRNP, providing new insights into the assembly of the spliceosome building blocks.

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.