Volume 17 Issue 4, April 2021

High-throughput biochemical and biological analyses of disease-associated histone mutations reveal key residues in globular cores that affect chromatin remodeling, nucleosome stability, and stem cell pluripotency.

Acyl protein thioesterases are critical regulators of S-acylation, removing acyl chains from dynamically S-acylated proteins. A cytosolic deacylase, APT2, is S-acylated by zDHHC3 and zDHHC7 and is predicted to deform the lipid bilayer to extract acyl chains, capturing them within a hydrophobic pocket.

A genetically encoded real-time redox reporter reveals that H₂O₂-signaling peroxiredoxin (PRX) proteins couple yeast metabolic oscillations with the cell division cycle. This new PRX function suggests fresh avenues for exploring circadian regulation of cell division and cancer.

This Perspective summarizes the known types of ligand-controlled ribozymes and riboswitches and discusses the reasons why allosteric ribozymes formed by fusion of RNA enzymes and RNA aptamers are rare in today’s biological systems.

The cryo-EM structures of Cas12g in complex with sgRNA in the absence and presence of target RNA reveal that the duplex formed by target RNA and crRNA binds to a central channel of Cas12g, inducing its conformational change and activation.

Bacteriophage single-stranded DNA annealing proteins (SSAPs) interact with the C termini of single-stranded binding proteins in host bacteria, a finding that enables engineering of enhanced SSAP portability and DNA recombineering activities.

Combined use of a DNA-barcoded nucleosome library and a humanized yeast library allows the identification of histone globular domain mutations that affect histone exchange and nucleosome sliding processes, as well as cancer-associated gene pathways.

Structural analysis of the A2058-dimethylated and unmethylated 70S ribosome complex alone and in combination with macrolides reveals the role of the desosamine moiety of macrolides in drug binding and resistance.

A synthetic protein quality control system (ProQC) uses RNA hybridization to enhance translation of full-length proteins in coupled transcription–translation systems to optimize production of biosynthetic enzymes for metabolic engineering efforts.

An engineered Pichia pastoris strain enables the synthesis of tryptophan C-mannosylated proteins, and selected monoclonal antibodies provide tools for detecting these modified proteins and studying their functions.

Acyl protein thioesterase APT2 interacts with membranes via its charged β-tongue, becomes palmitoylated by ZDHHC3/7 and deforms the bilayer to extract substrate acyl chains. APT2 deacylation leads to its membrane release and degradation.

The essential protein VCP/p97 regulates autophagosome formation by promoting the deubiquitinase activity of ataxin-3 toward Beclin-1 and also by regulating the assembly of the Beclin-1–PI3K complex I.

Dissection of the allosteric coupling in the cyclin-dependent kinase Cdk2 shows that this allostery explains how the kinase is activated by cyclin binding and phosphorylation and how it differentiates between Cdk2 and Cdk4 inhibitors.

Ca²⁺-independent phospholipase A₂β cleaves an oxidized form of phosphatidylethanolamine (PE) involved in ferroptosis such that increases in PE sensitize cells to ferroptosis. A mutant allele of the enzyme links neurodegeneration and ferroptosis.

Hydrogen peroxide and peroxiredoxin oxidation levels oscillate during the yeast metabolic cycle, while the absence of peroxiredoxins or the use of thiol oxidants and reductants disrupts metabolic cycling and its coupling with cell division.

Crystal structures of a cobalamin-dependent radical S-adenosylmethionine (SAM) methylase reveal an unexpected mechanism that involves substrate-assisted catalysis whereby the carboxylate group of the co-substrate SAM serves as a general base.

Beginning with a functional site and building a supporting scaffold around it enables the de novo design of proteins with distinct binding motifs for use in biosensors to detect antibody responses and as ligands of synthetic signaling receptors.