Research articles

The authors cloned anti-NMDAR (N-methyl-d-aspartate receptor) monoclonal antibodies from the immune B cells of persons with autoimmune encephalitis and revealed their precise binding epitopes on NMDARs and the pathological mechanism underlying the downregulation of synaptic function.

This work reveals structures of biotin-dependent carboxylases in different states, provides notable insight into their catalytic mechanism and may help the development of new drugs for the treatment of related diseases.

The study presents cryo-electron microscopy structures of human autophagy-related protein (ATG) 2A in complex with WD-repeat protein interacting with phosphoinositides 4 (WIPI4) and the ATG2A–WIPI4–ATG9A complex, providing insights into spatially coupled lipid transport and re-equilibration during autophagosome formation.

Using single-molecule techniques, the authors find that the methyl-CpG-binding protein MeCP2, whose mutations cause Rett syndrome, exhibits distinctive behaviors when bound to nucleosomes versus free DNA, thus directing its multifaceted functions on chromatin.

Here, the authors develop an assay to measure DNA supercoiling, revealing DNA supercoiling domains across the human genome that are modulated by topoisomerase and showing their colocalization with nuclear compartments and impact on gene expression.

Combining genome engineering, epigenomics and multiplex three-dimensional microscopy approaches, the authors show that PRE chromatin loops form a topological scaffold, restricting promoter–enhancer communication and contributing to enhancer–promoter specificity.

Using cryo-EM, the authors revealed structures of ESCRT-III superfamily member PspA and the molecular basis of structural plasticity that enables assembly modulations by the addition of nucleotides and targeted mutations.

Combining patch-clamp electrophysiology, molecular dynamics simulations, cryo-electron microscopy and imaging of neuronal synapses, the authors reveal how AMPA glutamate receptors are regulated by protons that are released from synaptic vesicles during signal transmission.

Here, using cryo-electron microscopy to study the structure of LRPPRC (leucine-rich pentatricopeptide repeat-containing protein) in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), mRNA and the mitoribosome, the authors show that LRPPRC facilitates mRNA handoff to the mitoribosome and regulates the expression of several mitochondrial genes.

Here, the authors report cryo-electron microscopy structures of Escherichia coli transcription–translation complexes containing the transcription–translation coupling factor RfaH, showing that RfaH physically bridges RNA polymerase and the ribosome.

Using cryo-electron microscopy, the authors deepen our mechanistic understanding of nascent leading-strand synthesis during human DNA replication and provide the basis for a proofreading mechanism in B-family replicative polymerases.

Using high-speed atomic force microscopy, the authors reveal the polymerization mechanism of VIPP1 into ESCRT-III-like filaments that adopt spiral and polygonal supramolecular structures.

Here, the authors show that cytoplasmic uridylyltransferases TUT7 and TUT4 bind let-7 pre-miRNA by alternative means in the absence and presence of Lin28A, which directly interacts with both RNA and enzyme to convert from a distributive to a processive mode of action.

Here the authors show that, upon embryo implantation, signaling triggers a large-scale rearrangement of protein–RNA interactions. Phosphorylated LIN28A reassembles onto the 3′ untranslated region termini of pluripotency-associated mRNAs, where it converges with the binding of poly(A)-binding protein and drives selective mRNA decay.

Here the authors establish that ploidy-to-cell size ratio is a highly conserved determinant of proteome composition. In both mammals and yeast, they find that growth in large cells is restricted by genome concentration as if it were a limiting nutrient.

Using cryo-electron microscopy, the authors obtained structures of Streptococcus pneumoniae nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in different states. Combined with site-directed mutagenesis and biochemical assays, the structures shed light on the activity and regulation of NADPH oxidases.

Li et al. reveal the mechanism by which the ribosome termination complex catalyzes dissociation of GDP from release factor RF3 in Escherichia coli. The findings explain the guanine nucleotide exchange factor activity of the ribosome.

This study reveals the mechanisms of NEAT1 lncRNA maturation and menRNA biogenesis and uncovers an RNA-centric, riboswitch-like mechanism where menRNA drives its own conformational isomerization that directs repeat CCA addition and rapid degradation.

Lavdovskaia, Hanitsch, Linden et al. provide a comprehensive roadmap of mitoribosome biogenesis and establish that mitochondria use a unique pathway for the assembly of their translation machinery.

The authors follow the folding dynamics of a nascent protein trapped during its synthesis, showing how the ribosome and a molecular chaperone shape the pathway of protein folding.