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Stalled bacterial ribosomes can be rescued by interaction with SmpB protein and a highly structured transfer-messenger RNA, and a cryo-electron microscopy map of this complex now shows how EF-G-dependent translocation of this non-canonical ligand is facilitated by conformational changes in the ribosome and the transfer-messenger RNA.

Eukaryotic initiation factor 5b (eIF5B) is essential for translation initiation. Spahn and colleagues now report cryo-EM structures of the mammalian 80S initiation complex associated with eIF5B that redefine eIF5B as a tRNA reorientation factor.

The conserved eukaryotic heterotrimeric NatC complex co-translationally acetylates the N-termini of numerous target proteins. Here, the authors provide insights into the catalytic mechanism of NatC by determining the crystal structures of Saccharomyces cerevisiae NatC in the absence and presence of cofactors and peptide substrates and reveal the molecular basis of substrate binding by further biochemical analyses.

During translation, tRNAs enter the ribosome and then move sequentially through three sites, known as A, P and E, as they transfer their attached amino acids onto the growing peptide chain. How the ribosome facilitates tRNA translocation between the sites remains largely unknown. Now a study uses multiparticle cryoelectron microscopy of a ribosome bound to the translation elongation factor, EF-G, to get information about tRNA movement. It identifies two new substates and sees that translocation is linked to unratcheting of the 30S ribosomal subunit.

The crystal structures and cryo-electron microscopy reconstructions of eEF3 on its own and attached to the ribosome are resolved, providing an insight into how eEF3 functions as a translation factor on the A and E sites on a ribosome.

The ribosomal GTPase, LepA or EF4, can promote back-translocation of tRNAs, thus reversing translocation. The cryo-EM structure of the ribosome with EF4 now suggests how such back-translocation can be allowed to occur and reveals that the tRNA is in an intermediate state that deviates from its canonical position.

Proline-rich antimicrobial peptides (PrAMPs) are inhibitors of bacterial protein synthesis. Here, the authors demonstrate that the antimicrobial peptide Api137 can disrupt assembly of the ribosomal 50S subunit by inducing misfolding of its components.

Direct visualization of short-lived intermediates during active protein synthesis remains challenging. Here, the authors structurally capture transient translation intermediates to uncover temporary disome formation during ribosome collisions.

Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.

Here the authors demonstrate how protein translation, controlled by Ire1α, regulates neuronal diversification in the developing neocortex.

Xue et al. visualize how the antibiotic chloramphenicol reshapes the translation landscape and induces ribosome collision in bacterial cells, illuminating its context-dependent action across atomic, molecular and cellular scales.

mRNA surveillance is essential to maintain homeostasis in eukaryotes and is activated by mRNAs lacking a stop codon. Here the authors describe a high resolution cryo-EM structure of a nonstop complex that shows how arrested ribosome recognition is achieved during Dom34-mediated mRNA surveillance.

The production of ribosomes is a precisely orchestrated energy consuming cellular process of highest priority. Here, the authors use cryo-EM to show that bacterial ribosomal subunits, self-assembled from their purified RNA and protein components, mature along parallel pathways.

Two-pore channel 2 has been implicated in coupling changes in cellular energy status with endolysosomal function. Grimm et al.show that mice lacking this channel display defects in endolysosomal trafficking of LDL-cholesterol and are susceptible to hepatic cholesterol overload and fatty liver disease.

The authors perform parallel transcriptome sequencing, tRNA qPCR array, ribosome profiling and mass spectrometry across five stages of mouse neocortex development to model the dynamic transcriptome-to-proteome transition, discovering a critical prenatal window during which translational control is predominant.

Cryo-electron microscopy and single-molecule fluorescence methods are used to elucidate the mechanism of early translocation events on the bacterial ribosome.

The prenyl-binding protein PrBP/δ is a solubilization factor involved in trafficking of prenylated proteins. Here the authors present the ligand-free apo-PrBP/δ structure and propose a "solubilization by depletion" mechanism, where PrBP/δ sequesters only soluble rod photoreceptor phosphodiesterase (PDE6), leading to a dissociation of membrane-bound PDE6.

Packing nanoparticles into ordered superstructures finds applications in photonic materials, but fabrication over large scales is challenging. Zhao et al. show a roll-to-roll approach to prepare flexible films of ordered polymer nanoparticles via an oscillatory shear-induced structural transition.

A 2.2 Å cryo-electron microscopy structure of an actively translating 80S ribosome from tobacco reveals bound tRNA and mRNA, the nascent peptide and numerous cofactors, providing a basis for understanding the molecular mechanism of protein synthesis in plants.

Deep learning holds a great promise for the discovery and design of bioactive peptides, but experimental approaches to validate candidates in high throughput and at low cost are needed. Here, the authors combine deep learning and cell free biosynthesis for antimicrobial peptide (AMP) development and identify 30 functional AMPs, of which six with broad-spectrum activity against drug-resistant pathogens.

To date, patients still succumb to cancer, due to tumors not responding to therapy or ultimately acquiring resistance. Here the authors show that by exploiting patient derived organoids and a treatment-naïve patient derived xenograft, patient therapy can be personalized.

Structural characterization sheds mechanistic insights behind λN-dependent processive antitermination.

The cryo-EM structure of the γ-tubulin ring complex (γ-TuRC) from Xenopus laevis provides insights into the molecular organization of the complex, and shows that actin is a structural component that is functionally relevant to microtubule nucleation.

Eps15-homology domain containing proteins comprise a family of dynamin-related ATPases. Here, Melo et al. use cryo-electron tomography to determine the membrane-bound EHD4 structure, therefore clarifying the membrane binding and oligomerization mode.

Radiation therapy combined with androgen-deprivation therapy has become the standard-of-care treatment for patients with high-risk prostate cancer; however, superiority of this approach over other therapeutic options, such as surgery, has not been clearly demonstrated. This Review provides a comprehensive overview of the current status of surgery in the treatment of high-risk prostate cancer and highlights the findings that might underlie the increasing use of radical prostatectomy as the first-line treatment among patients with this disease.

In this Review, Nierhaus and colleagues discuss the recent structural and mechanistic insights that have improved our understanding of elongation factor G (EF-G)-mediated forward-translocation and EF-4-mediated back-translocation on the bacterial ribosome.