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Programmed ribosomal frameshifting (PRF) is an alternative translation strategy that causes controlled slippage of the ribosome along the mRNA, changing the sequence of the synthesized protein. Here the authors provide a thermodynamic framework that explains how mRNA sequence determines the efficiency of frameshifting.

The rapid temperature drop during plunge-freezing affects the structural ensembles obtained by cryo-EM. To quantify the extent of perturbation, Bock and Grubmüller combined continuum calculations, MD simulations, and kinetic models.

ER membranes tune protein degradation to lipid composition. Using reconstitution approaches, the authors show that the ubiquitin conjugating enzyme UBE2J2 senses lipid packing, modulating its own and partner enzyme activities; together, they integrate lipid saturation and cholesterol signals.

Ubiquitination is a versatile modification system in eukaryotic cells. Here, the authors unveil that the ubiquitin ligase HUWE1 can modify drug-like small-molecule substrates, beyond proteins. This discovery may be harnessed to develop specific tool substrates or inhibitors of HECT-type ligases.

The EMDataResource Ligand Model Challenge aimed at assessing the reliability and reproducibility of modeling ligands bound to protein and protein–nucleic acid complexes in cryo-EM maps determined at near-atomic resolution. This analysis presents the results and recommends best practices for assessing cryo-EM structures of liganded macromolecules.

Using atomic force microscopy, Pan et al. show that cyclic nucleotide-gated ion channel SthK, which can be differentially activated by cAMP and cGMP, binds both cyclic nucleotides but only cAMP can access a deep-bound state that could be essential for cAMP-dependent channel activation.

An all-atom protein force field, CHARMM36m, offers improved accuracy for simulating intrinsically disordered peptides and proteins.

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.

Proteins need to overcome energy barriers to induce intermediate steps in membrane fusion. Using lipid vesicles in which progression to hemifusion is arrested, the authors show that the metastable intermediate is enhanced by divalent cations and is characterized by the absence of proteins and local membrane thickening. Simulations reveal that thickening is induced by dehydration of the membrane surface.

The measles virus relies on the intrinsically disordered domain of its nucleoprotein, N_TAIL, to bind the polymerase complex responsible for viral transcription and replication, but the role played by disordered regions away from the binding site is not clearly understood. Here, through a combination of experiments and simulations, the authors show that transient and non-local interactions between disordered regions distant in sequence influence the conformational preferences of the binding sites and the folding and availability of its molecular recognition element, affecting viral replication kinetics.

Here the authors present the high-resolution structures of 17 antibiotics bound to Escherichia coli ribosomes, which may inform the development of new antibacterial agents. Their results unveil a conserved manner of antibiotic binding to the ribosome, including ordered water molecules.

Macrolides and ketolides antibiotics selectively interfere with the translation of a specific subset of proteins. Here the authors show how the macrolide erythromycin and the ketolide telithromycin interplay with the nascent polypeptide chain to arrest translation.

The structures of several states on the pathway of SelB-mediated delivery of selenocysteine-specific tRNA to the ribosome in Escherichia coli reveal the mechanism of UGA stop codon recoding to selenocysteine and show how codon recognition triggers activation of translational GTPases.

Synaptotagmin-1 is known to accelerate membrane fusion during neuronal exocytosis in response to Ca²⁺, but how it does this is unclear. By probing the activity of synaptotagmin-1 under conditions of low ionic strength, it is now shown that SNARE-mediated fusion is dependent on synaptotagmin-1, which tethers liposomes together but at distances too far for fusion. Ca²⁺ then induces synaptotagmin-1 to bring the liposomes closer together, allowing fusion to proceed.

Using 13 intermediate-translocation-state models derived from X-ray and cryo-EM structures of Escherichia coli ribosomes to guide large-scale molecular dynamics simulations, a new study now models the path taken by tRNAs during spontaneous translocation to uncover the mechanisms that facilitate tRNA movement through the ribosome.

When the antibiotic erythromycin is bound to the ribosomal exit tunnel, ErmBL peptide translation stalls and allows translation of the downstream methyltransferase ErmB. Here the authors combine cryo-EM and molecular dynamics simulations to identify the underlying basis for the inhibition of peptide bond formation that results in ribosome stalling.

Clustering of proteins in the plasma membrane plays an important role in the regulation of both cellular signalling and membrane remodelling. Milovanovic et al.demonstrate that mismatch between transmembrane domain length and the lipid bilayer thickness is sufficient to drive clustering of SNARE proteins.

Existing methods to extract structural information from single-molecule scattering measurements require large number of photons per image. Here the authors discuss a method to reconstruct the structure of a molecule from X-ray scattering data by using only three photons per image.

Interactions between synaptotagmin-1 and the SNARE syntaxin-1 are known to mediate synaptic-vesicle exocytosis. Fusion experiments with artificial lipid membranes combined with the crystal structure of synaptotagmin's C2B domain bound to phosphoserine indicate that PIP2 clusters, organized by syntaxin, act as molecular beacons for vesicle docking and direct Ca²⁺-dependent membrane fusion.

In the Big Data era, a change of paradigm in the use of molecular dynamics is required. Trajectories should be stored under FAIR (findable, accessible, interoperable and reusable) requirements to favor its reuse by the community under an open science paradigm.

In vitro and in silico analysis enables the rational design of fatty acid synthase (FAS)-mediated pathways for the compartmentalized production of desirable fatty acids and a polyketide lactone.