Volume 29 Issue 6, June 2022

MFSD2A mediates uptake of the essential fatty acid DHA across the blood–brain barrier. Separately, via interactions with syncytin-2, MFSD2A contributes to the formation of the mother–fetus placental boundary. Cryo-EM analysis of a human MFSD2A–syncytin-2 complex provides new insights into how MFSD2A performs these dual roles.

Furukawa and colleagues use cryo-EM, molecular dynamics simulations, and electrophysiology to dissect the binding sites of the clinically important channel blockers phencyclidine, ketamine, and memantine to NMDA receptors, providing a blueprint for improved therapeutics.

Cryo-EM, biochemical and cell-based assays reveal strong allosteric autoinhibition of the actin-binding domains of plastins. Physiological tuning of this engagement explains the plastins’ ability to organize actin assemblies of different morphologies.

Murray et al. report an approach to identify pathogenic mutations in low-complexity-domain-containing proteins that lead to the formation of amyloid aggregates. Among those characterized are keratin-8 mutations associated with liver disease, linking amyloid aggregation to liver pathology.

Arrigoni et al. present non-canonical voltage-gated ion channel pore domain (PD) structures demonstrating that the PD is an autonomously folded unit found in diverse proteins and show that PDs can adopt non-canonical forms in full-length channels.

Circadian clocks both instruct and follow the epigenome. New data reveal that the core-clock PERIOD complex shapes genomic H2A.Z landscapes. H2A.Z, in turn, plays an essential role in rhythm generation by regulating BMAL1 stability.

Here the authors build different regulatory landscapes in an inactive chromatin environment and observe that enhancers can both carry out their classic role of stimulating transcription initiation and elongation at target gene promoters and recruit cohesin to create contact domains, engage CTCF sites and activate distant genes.

Here, authors use targeted degradation and Hi-C in eukaryotic cells to show that acetylation of the cohesin subunit Smc3 stops loop extrusion during DNA replication by recruiting Pds5, also required for sister chromatid cohesion, and by preventing Scc2-dependent loop expansion.

Here, the authors use gene editing combined with Hi-C to show that cohesin acetylation restricts the length of chromatin loops through enhanced binding of cohesin to PDS5A.

Functional and structural characterization of rhodopsin-bestrophin fusion proteins from marine algae unveils the existence of giant light-sensitive anion channels with unusual biophysical properties.

Major facilitator superfamily protein MFSD2A takes essential omega-3 fatty acids into the brain, and is the receptor of SYNC2 membrane fusogen in placenta. A cryo-EM structure of the human MFSD2A–SYNC2 complex reveals key aspects of MFSD2A transport and receptor mechanisms.

Here the authors present the INSERT-seq methodology to investigate the effect of transcribed sequence on processive transcription. The authors find that GC content and splice site sequences are important determinants of elongation potential.