Two new papers describe the successful purification of the partially intact human native red blood cell band 3 multiprotein membrane complexes, providing information that the authors then use to capture the structures and interactions of multiple erythrocyte proteins using high-resolution cryo-EM.

Structural maintenance of chromosomes (SMC) complexes such as condensin regulate chromosome organization by extruding loops. A new study uses single-molecule imaging of condensin on supercoiled DNA to understand how condensins navigate the under- and overwound DNA states common throughout the genome.

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.

Elango et al. identify a new class of substrates on which the Fanconi anemia SLX4–XPF nuclease operates to mediate homologous recombination at DNA–protein replication fork barriers and promote cellular tolerance of DNA–protein cross-links.

An endogenous proteasome inhibitor was identified 30 years ago, but its mechanism remained unclear. Rawson et al. show that this inhibitor is present within the interior of the proteasome, where it simultaneously inhibits all six active sites.

Functional assays and cryo-EM structures show that ubiquitin binding and a cofactor drive protein quality-control client selection by the hybrid E2/E3 enzyme UBE2O.

Here, the authors find that histone demethylase Epe1-mediated stress resistance is regulated by proteasome-dependent truncation, allowing heterochromatin to reprogram gene expression that confers antifungal resistance to some fission yeast cells in the population.

Cryo-EM, X-ray crystallography and crosslinking mass spectrometry are harnessed to solve the structure of the full-length Rho-GEF P-Rex1, uncovering a two-layered mechanism of autoinhibition released upon Gβγ and PI(3,4,5)P3 binding.

This work reveals the structural and biochemical basis for phosphorylation-dependent day/night signaling by KaiC in the cyanobacterial circadian clock.