Research articles

Different patterns of nucleosome exposure by developmentally indispensable pioneer transcription factors and enabling of a nucleosome remodeler complex reveal mechanisms of gene regulatory initiation within compacted chromatin.

GPAT1 is a mitochondrial outer membrane protein that catalyzes the first step of glycerolipid biosynthesis. Cryo-EM structures and functional studies of human GPAT1 uncover the molecular architecture and mechanism of this important acyltransferase.

The structure of a heteromeric volume-regulated LRRC8A/C channel shows a hexameric assembly of four clustered A subunits interspersed by two C subunits, which increase the mobility of the protein, thus facilitating channel activation.

The mechanism controlling SWI/SNF chromatin remodeler targeting is incompletely understood. This study demonstrates that AP-1 transcription factors guide SWI/SNF to genomic regions, resulting in 3D genomic architecture alterations.

ABC-type heterotrimeric proteins can be designed de novo using coiled coils and helical bundles as starting scaffolds, extended using helical repeat proteins and then used as building blocks for higher-order oligomeric assemblies.

LRRK2 is one of the most commonly mutated genes in familial Parkinson’s disease. Here, the authors report a cryo-EM structure of the catalytic half of LRRK2 bound to microtubules, revealing determinants of binding that are independent of LRRK2 kinase activity.

Here the authors show that DNMT3A and DNMT3B are differentially regulated during endoderm and mesoderm differentiation in mouse development and characterize the dynamic DNMT3A and DNMT3B sequence specificity during gastrulation.

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.

The authors describe how three types of cis-element (CTCF sites, active TSSs and TTSs) regulate cohesin trafficking along chromosomes. They uncover that this cohesin traffic pattern is genetically linked to gene regulation and RNA processing.

Cruz et al. present cryo-EM structures of large ribosomal subunit assembly intermediates that reveal how the DEAD-box helicase Spb4 remodels rRNA secondary structures to facilitate and guide 60S maturation.

Basu and colleagues comprehensively characterize how sequence and epigenetic modifications impact the local mechanical properties of DNA. The results suggest that DNA mechanics may have evolved to aid diverse DNA-deforming biological processes.

Here the authors use cryo-EM and biochemical analysis to show how the ancillary protein TPR-CHAT regulates the nuclease function of the CRISPR-guided nuclease Cas7-11.

Hall et al. discovered the molecular mechanism for the polarity of the CRISPR roadblock to transcription: RNA polymerase progression can collapse the R-loop formed by a bound dCas to allow read-through from the PAM-distal side. Guide RNA modifications allow modulation of the dCas R-loop stability.

This work provides molecular insights into the export of cyclic glucans by a bacterial ABC transporter. The findings expand our understanding of polysaccharide trafficking across bacterial membranes, as well as protein-sugar interactions in general.

Rengachari et al. provide a structural investigation of Pol II initiation at snRNA gene promoters and find that the snRNA-activating protein complex enables DNA opening and transcription initiation independent of TFIIE and TFIIH in vitro.

The voltage-gated sodium channel Na_V1.7 plays essential roles in pain sensation. The authors report cryo-EM structures of Na_V1.7 in complexes with three pore blockers, elucidating distinct mechanisms of action of their modulation on Na_V1.7.

Cryo-EM structures of the transcription preinitiation complex in the presence of the +1 nucleosome show how the general transcription factor TFIIH can interact with the nucleosome at several positions.

Cryo-EM has facilitated structural studies of membrane proteins, but inactive GPCRs have remained inaccessible due to their small size. Robertson et al. demonstrate a common nanobody-based approach to streamline the determination of such structures.

Luan et al. find that CTCF shapes the transcriptional landscape in part by suppressing the initiation of upstream antisense transcription at hundreds of divergent gene promoters.

Schmidpeter and colleagues showed that anionic lipids bind to pacemaker ion channels and increase their activity by acting like keys that unlock salt bridges at the channel gates.