Articles

Xu et al. establish the importance of H2A.Z in mouse oocyte development. H2A.Z is incorporated into chromatin at promoters and putative enhancers, and its presence promotes histone acetylation in fully grown oocytes.

Here, Rangan et al. characterize S. cerevisiae intron structures with in vivo transcriptome-wide structure probing, showing that certain introns exhibit structural features that distinguish pre-mRNA from spliced mRNA and contain structures that regulate gene expression.

Here the authors uncover how a floppy tail in a protein acts as a remote switch, flipping activity on or off by tweaking internal motion, which reveals a powerful new way proteins regulate themselves without direct contact.

Guided by a structure of VGLUT2 with substrate, Li et al. identify the mechanisms for selective substrate recognition, a role for lipid modification in limiting axonal dispersion and for the cytoplasmic gate in allosteric regulation by lumenal H⁺.

Schweighauser, Shi, Murzin and colleagues report cryo-EM structures of tau filaments from individuals with P301L or P301T MAPT mutations. P301L tau filaments adopted a distinct three-lobed fold, while P301T filaments had either a variant of the three-lobed fold or a V-shaped fold.

Segura-Covarrubias et al. provide structures of kainate-type ionotropic glutamate receptors in ligand-free and partial agonist-bound conformations. They describe a gating switch upon desensitization and the allosteric modulation of N-glycosylation, which interferes with cation binding.

Autophagy is initiated by the Unc-51-like kinase protein kinase complex (ULK1C) and class III phosphatidylinositol 3-OH kinase complex I (PI3KC3-C1). Here, the authors reveal the structure of the 2:1:1 core of ULK1C and its complex with PI3KC3-C1. ULK1C transitions to a 2:2:2 complex in the presence of PI3KC3-C1, suggesting a mechanism for autophagy induction.

Nodelman, Folkwein et al. define a regulatory region in Chd1 containing adjacent inhibitor and activator elements that compete for binding to the remodeler ATPase. The competition between these elements shows how remodeler regulation is integrated into the nucleosome sliding cycle.

Using biochemistry, chemical biology, and cryo-EM, Maiwald et al. elucidate how TRIP12 forms K29 linkages and K29/K48-linked branched ubiquitin chains, revealing a mechanism for polyubiquitylation shared by some HECT E3s.

Zhao et al. show that Akt-mediated phosphorylation of ubiquitin-fold modifier 1 (UFM1)-specific E3 ligase 1 (UFL1) catalyzes the UFMylation of ArpC4, a core subunit of actin-related proteins 2 and 3. Through ArpC4 UFMylation, UFL1 promotes lamellipodia formation and enhances cell migration, invasion and metastasis.

Here Yeow et al. present a model in which TRIM37 regulates microtubule-organizing centers through substrate-templated activation, providing a unifying mechanism for the control of mesoscale assemblies by the TRIM family of E3 ligases.

Bellaart et al. address how the ubiquitin ligase tripartite motif-containing protein 37, the gene for which is mutated in Mulibrey nanism, uses peptide motif recognition and substrate-directed oligomerization to prevent the formation of ectopic spindle poles that cause chromosome missegregation.

Using cryo-EM, Kendrick et al. reveal multiple dynein conformations during dynein’s mechanochemical cycle and Lis1 binding that represent intermediate states of dynein’s activation.

Kucharska, Ivanochko and Hailemariam and colleagues solved cryo-EM structures of Pfs48/45, needed for Plasmodium falciparum development, with potent antibodies. The work revealed conformational epitopes, with implications for design of therapies against malaria.

Here the authors demonstrate that the assembly of mitochondrial respiratory supercomplex (III₂–IV) from Toxoplasma gondii is critical for parasite fitness. They reveal the basis for cytochrome b inhibition by atovaquone and improved ELQ inhibitors.

DEK, a chromatin-associated oncoprotein, regulates chromatin dynamics and cell fate. This study reveals the structural basis of DEK’s interaction with nucleosomes, showing its role in maintaining embryonic stem cell identity by modulating H3K27me3.

Here Tai et al. unveil elevated formation of the C-terminal binding protein (CtBP)–tripartite-motif-containing protein 28 (TRIM28) complex in breast cancer cells and mutual protection between CtBP and TRIM28. This complex is required for mammary gland development and its high levels lead to breast cancer metastasis by repressing autophagy.

Karpinska, Zhu and colleagues characterize the structure-function relationship of the genome during cellular differentiation and demonstrate a role for enhancer-promoter interactions in gene regulation that is independent of cooperative interactions in chromatin hubs.

Kazi et al. report the crystal structure of the mitochondrial deubiquitinase USP30, a clinical stage Parkinson’s disease drug target, in complex with a specific inhibitor. The authors delineate a framework for specific deubiquitinase inhibition.

Piwi-interacting RNAs (piRNAs) are vital for genome integrity and fertility. Here the authors reveal that spatial clustering of piRNA genes in Caenorhabditis elegans promotes transcription through phase separation and deSUMOylation, uncovering a SUMOylation-regulated mechanism for piRNA production in heterochromatic genomes.