Volume 30 Issue 2, February 2023

Craspase is newly identified type III CRISPR–Cas system with two major components: the nuclease Cas7-11, and the protease TPR-CHAT. Craspases perform a delicate balancing act between nuclease and protease activity to achieve immune tolerance and defense in bacteria, and show promise as highly regulatable genome-editing tools.

AlphaFold2 has already changed structural biology, but its true power may lie in how it changes the way we think about cells and organisms. Two studies broadly assess its utility and limitations in providing structural models to shed light in areas such as mutations, protein–protein interactions, and phosphorylation.

Gene transcription initiation is a highly regulated process in which Pol II and general transcription factors assemble into a pre-initiation complex. Structural studies of yeast and human initiation complexes shed light on the role of the first nucleosome flanking gene promoters in controlling the transcription machinery.

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.

Cryo-EM structures of human DNA-dependent protein kinase in intermediate and active states reveal the molecular mechanism of the allosteric activation of the atypical kinase complex, explaining why it is DNA dependent.

Tan et al. found that topoisomerase-independent DNA nicking is required for most, if not all, signal-induced acute enhancer activation programs, nucleating formation of a Ku70–HP1γ–Med26 complex required to facilitate transcriptional activation.

The cryo-EM structure of unliganded mouse NAIP5 reveals the mechanism for NAIP—NLRC4 inflammasome activation in which ligand binding drives a roughly 20° rotation in the WHD–HD2–LRR domains, resulting in the formation of a steric clash to activate NLRC4 and generating new interactions to stabilize the NAIP5–NLRC4 complex.

Moss and colleagues use cryo-EM, brominated lipid probes and molecular dynamics simulations to reveal how membrane curvature stress imposed by membrane-remodeling ESCRT-III proteins alters membrane structure by deforming polyunsaturated lipids.

The sorting and assembly machinery (SAM) mediates mitochondrial β-barrel protein folding and membrane insertion. A cryo-EM structure of the yeast SAM complex bound to an early eukaryotic β-barrel intermediate reveals a multipoint guidance mechanism.

SYCP1 structures are conformationally remodeled by molecular adapter SYCE3 to assemble into the supramolecular synaptonemal complex that mediates chromosome synapsis and facilitates crossover formation in meiosis.

Comprehensive poly(A)-inclusive RNA isoform sequencing throughout the human oocyte and preimplantation embryo development reveals poly(A)-tail-mediated maternal mRNA remodeling that is essential for human embryo development.

Here the authors explore the ability of AlphaFold2 to predict structures across the human protein-protein interactome and the limitations thereof.

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.